Mol Divers DOI 10.1007/s11030-015-9576-4

FULL-LENGTH PAPER

A facile tandem Michael addition/O-cyclization/elimination route to novel chromeno[3,2-c]pyridines Remani Vasudevan Sumesh · Akilan Malathi · Raju Ranjith Kumar

Received: 29 October 2014 / Accepted: 22 February 2015 © Springer International Publishing Switzerland 2015

Abstract A facile and efficient synthesis of a library of novel chromeno[3,2-c]pyridines has been achieved from the reaction of various 3,5-((E)-arylidene)-1-alkylpiperidin4-ones and cyclic 1,3-diketones. The reaction presumably occurred via tandem Michael addition–intramolecular Ocyclization–elimination sequence in a single operation. Keywords Tandem reaction · 3, 5-((E)-arylidene)-1alkylpiperidin-4-one · Cyclic 1, 3-diketone · Michael addition · Chromeno[3, 2-c]pyridine

Introduction Chromenopyridines are versatile class of organic compounds falling under the notion of “privileged medicinal structures” [1]. Amlexanox 1 is an antiallergic and antiulcer agent, whereas compounds 2, 3 and 4 inhibit mitogen-activated protein kinase-activated kinase 2, histamine-stimulated gastric acid secretion in animals and selective D4 receptor antagonist, respectively [2–5] (Fig. 1). In addition, chromenopyridine derivatives have also been reported to display antiproliferative [6], cancer chemopreventive [7], anti-bacterial [8,9] and anti-asthmatic activities [10]. Consequently, incessant efforts have been dedicated towards the synthesis and biological evaluation of these heterocycles. In general,

chromenopyridine scaffolds have been synthesized employing coumarins, chromones, salicylaldehyde or 3-carbethoxy4-piperidone [11–25]. In the present work, we report for the first time the synthesis of chromeno[3,2-c]pyridines 9 from the tandem reactions of 3,5-((E)-arylidene)-1-methylpiperidin-4-ones 7 and cyclic 1,3-diketones 8 (Scheme 1). A related protocol has been reported previously by Mallik et al. [26] wherein the synthesis of octahydroxanthenes has been achieved in 34–70 % yields from the reaction of E,E − α,α -diarylidenecyclohexanones and cyclohexane1,3-dione in the presence of amberlyst-15 under reflux for 16 h. However, the protocol reported in the present work is more advantageous over the literature method with respect to yield, time and isolation of the product. Incidentally, tandem reactions have emerged as a powerful tool for the construction of complex heterocycles and natural products [27–33]. These protocols comprise transformation of two or more bond-forming reactions under identical conditions, in which the latter transformations take place at the functional groups obtained in the former bond-forming or bond-breaking reactions, without the isolation of the intermediates or addition of any further reagents or catalysts [34– 38]. The present investigation also stems from our constant effort in synthesizing structurally diverse novel heterocycles employing tandem/domino processes [39–43].

Results and discussion Electronic supplementary material The online version of this article (doi:10.1007/s11030-015-9576-4) contains supplementary material, which is available to authorized users. R. V. Sumesh · A. Malathi · R. Ranjith Kumar (B) Department of Organic Chemistry, School of Chemistry, Madurai Kamaraj University, Madurai 625 021, Tamil Nadu, India e-mail: [email protected]

Initially, we investigated the three-component reactions of N -methyl-4-piperidone 5, 4-methoxybenzaldehyde 6 and cyclohexane-1,3-dione 8a (Scheme 2) in ethanol in the presence of various bases. In all these cases, 9-(4-methoxyphenyl)3,4,5,6,7,9-hexahydro-1H-xanthene-1,8(2H)-dione 10 was isolated exclusively in quantitative yields, whereas the

123

Mol Divers

O

O

O

N

NH2

N

SR

NH2

CO2H

Ph

CN O

1

N

NH2

O

2

O

N

O

3

O

4

Fig. 1 Chromenopyridine drugs Scheme 1 Synthesis of chromeno[3,2-c]pyridines 9

O R2 O

N R1 5

O 2 R2CHO 6 NaOH, EtOH rt, quantitative

R2

3

R R2

N R1 7

5

O

R3

4 4a

3

8 AcOH, reflux 12 h

R1

N 2

1

10a

O

R3

6

5a

R3

7 10

9

9a

2

R

8

O

9

Scheme 2 Three-component reaction

MeO

5

X

4 4a

3

N 2

1

10a

O

5a

6 7

10

9a

8

9

O O

O

MeO O

N

conditions

CHO 6

9, not formed OMe OMe

5

8a O

O

1 2 3

9

8

8a

7

9a 4

10a 4a

O10

6

5

10, quantitative expected chromeno[3,2-c]pyridine 9 was not formed. The structure of 10 was elucidated with the help of NMR spectroscopy wherein the 9-CH and OMe protons appeared as singlets at 4.76 and 3.74 ppm, respectively. The 2, 3 and 4-CH2 protons were observed as multiplets in the range 1.91–2.68 ppm, and the two doublets at 6.76 and 7.21 ppm (J = 8.7 Hz) were due to the o-and m-CH protons of the phenyl ring, respectively. Presumably, the Knoevenagel condensation of 6 and 8 afforded the intermediate 11, which preferentially underwent Michael addition with another molecule of 8a rather than 5 forming 10 (Scheme 3). Further, the reaction

123

of 8a and 6 was performed with a view to isolate the intermediate 11 and then carry out Michael addition with 5 in a separate reaction. However, the above reaction afforded 10 in quantitative yields within 10 min as observed in the threecomponent version. We then synthesized 3,5-bis((E)-4-bromobenzylidene)1-methylpiperidin-4-one 7h from the reaction of 5 and p-bromobenzaldehyde following literature procedure [44]. Subsequently, the reaction of 7h and cyclohexane-1,3-dione 8a affording chromeno[3,2-c]pyridine 9h was investigated under various conditions (Scheme 4). Initially, the reaction of

Mol Divers Scheme 3 Plausible mechanism for the formation of 10

O 6 O

O

Ph H

O

O

Ph

Knoevenagel -H2O

Ph

Michael

O

O

O

8a

O

O 8a OH 12

11

O-cyclization O

Ph

O

O

Ph

H

O

Elimination -H2O

O

O

Scheme 4 Synthesis of chromeno[3,2-c]pyridine 9h

OH

13

10

Br

Br

O

CHO O Br

NaOH, EtOH rt, quantitative

N

O

6h

O O 8a N

conditions

N

O

5 9h

7h

Br

Br

Entry

Reaction condition

Yield of 9h (%)

1

Ethanol, DEA, reflux, 12 h

0a

2

Ethanol, TEA, reflux, 12 h

0a

3

Ethanol, DIPEA, reflux, 12 h

0a

4

Ethanol, piperidene, reflux, 12 h

0a

5

Ethanol, pyridine, reflux, 12 h

0a

6

Ethanol, InCl3, reflux, 12 h

0a

7

Ethanol, PTSA, reflux 12 h

45

8

Water, AcOH (30 mol%), reflux 12 h

30

9

Water, AcOH (1:1) reflux, 12 h

99b

10

AcOH, reflux 12 h

99b

a

Reaction failed to occur; bQuantitative yields were obtained

123

Mol Divers

7h and 8a was performed in refluxing ethanol in the presence of different bases, but these reactions failed to occur (Scheme 4, entries 1–5). We then tried this reaction in acidic conditions and observed that in the presence of p-tolunesulfonic acid the reaction afforded 9h in a moderate yield of 45 % (Scheme 4, entry 7). Further, the above reaction was investigated in water in the presence of catalytic amount of acetic acid wherein 30 % of 9h was isolated. However, quantitative yield of 9h was obtained when the reactants were refluxed overnight either in 1:1 water:acetic acid mixture or acetic acid. After completion of the reaction, the mixture was poured into water and neutralized with saturated sodium bicarbonate solution to obtain the product as precipitate, which was filtered and washed with n-hexane to obtain pure 9h. The optimal reaction condition thus established was then employed for library construction with several N -substituted 3,5-bis((E)-arylidene)-piperidin-4-ones 7 and cyclic 1,3diketones 8 (Scheme 1 and Table 1). A total of fifty four chromeno[3,2-c]pyridines 9a–9aab were synthesized in quantitative yields. It is noteworthy that the reaction proceeded smoothly with 7 bearing electron-withdrawing or electron-donating groups in the aryl rings affording 9 in quantitative yields. Further, the presence of sterically hindered groups in the aryl rings and bulky bis naphthyl in 7 also had no adverse effects in the yield of 9. The quantitative yields of chromeno[3,2-c]pyridines 9 in conjunction with high atom economy (since water is the only by-product) render this protocol atom efficient and green. The structure of all the chromeno[3,2-c]pyridines 9a– 9aab is in complete agreement with the elemental analysis, ESI mass, IR and NMR spectroscopic data as elucidated for 9h. The mass spectrum of 9h showed a characteristic m/z signal at 542.05. The IR spectrum of 9h showed strong absorption at 1626 and 1662 cm−1 due to the α,β-unsaturated carbonyl and C–C groups, respectively. In the 1 H NMR of 9h, a singlet at 4.23 ppm was readily assigned to CH-10 proton on the basis of its multiplicity. From the C,H–COSY correlation of the above singlet, the signal at 37.7 was assigned to C-10. Further, 10-CH proton showed HMB correlations with the C-9 carbonyl carbon at 197.1 ppm, ipso carbons at 165.6, 140.5, 115.0 and 113.4 ppm due to C-5a, C-4a, C-10a and C9a, respectively and a CH2 carbon at 55.2 assignable to C-1. From the C,H–COSY correlation of this carbon signal, it was evident that the two doublets at 2.81 and 2.99 ppm (J = 16.5 Hz) were due to 1-CH2 protons. The 3-CH2 protons appeared as doublets at 3.35 and 3.51 ppm (J = 14.1 Hz) and the C,H– COSY spectra revealed that the signal at 54.4 ppm was due to C-3. The 6, 7 and 8-CH2 protons appeared as multiplets in the range 1.91–2.67 ppm, whereas the carbons appeared at 27.5, 20.3 and 36.8 ppm, respectively. The benzylidene and the N–CH3 protons appeared as singlets at 6.89 and 2.28 ppm, respectively. The complete assignment of 1 H and 13 C chemical shifts of 9h is given in Fig. 2.

123

1.91-2.09, m 2.61-2.67, m 20.3 27.5

2.32-2.37, m 36.8

6.89, s, 121.7 7.09, d, J = 8.4 Hz 130.0

165.6

H 142.5

7.48, d, J = 8.4 Hz 121.1 Br 131.5

3.35, d, J = 14.1 Hz 3.51, d, J = 14.1 Hz 54.4

Fig. 2

1H

H

O 140.5

H

127.7

115.0

N CH3 2.28, s 44.6

4.23, s 37.7

197.1

O H H

113.4

7.18, d, J = 8.4 Hz 130.6

135.2

H 120.6

7.39, d, J = 8.4 Hz 131.4

Br 2.81, d, J = 16.5 Hz 2.99, d, J = 16.5 Hz 55.2

and 13 C NMR chemical shifts of 9h

A plausible mechanism for the formation of chromeno [3,2-c]pyridines 9 involving a tandem transformation is depicted in Scheme 5. This reaction is triggered by an initial Michael addition of cyclic 1,3-diketones 8 over the 3,5-((E)-arylidene)-1-alkylpiperidin-4-ones 7 to afford the intermediate 14, which then undergoes an intramolecular O-cyclization to form the intermediate 15. Apparently, 15 undergoes dehydration resulting in the formation of chromeno[3,2-c]pyridines 9.

Conclusions The present work reported an efficient synthesis of a library of novel chromeno[3,2-c]pyridines from the reaction of various 3,5-((E)-arylidene)-1-alkylpiperidin-4-ones and cyclic 1,3-diketones in acetic acid. The reaction presumably occurred through a tandem Michael addition–intramolecular O-cyclization–elimination sequence of reactions in a single operation affording the products in quantitative yield.

Experimental General experimental The melting points were measured in an open capilary tubes and are uncorrected. Electronspray ionization mass spectrometry (ESI–MS) analyses were recorded in LCQ Fleet, Thermo Fisher Instrument in negative ion mode. The collision voltage and ionization voltage were –70 V and –4.5 kV, respectively, using nitrogen as atomization and desolvation gas. The desolvation temperature was set at 300 ◦ C. The scan range of mass spectrum was 300–2000 m/z. The relative amount of each component was determined from the LC-MS chromatogram, using the area normalization method. Infrared spectra were recorded on a SHIMADZU FT-IR instrument using KBr pellets. Elemental analyses were performed on Perkin Elmer 2400 Series II CHNS analyzer. The

Mol Divers Table 1 Diversity of substrates

R2 5

3

R1

4 4a

N 2

1

O

R3

7 10

10a

9

R3

6

5a

9

9a

R2

8

O

Entry

Comp 9

R1

R2

R3

Yield (%)a

mp (◦ C)

1

a

Me

C6 H5

H

99

76–77

2

b

Me

2-ClC6 H4

H

98

87–88

3

c

Me

4-ClC6 H4

H

96

92–93

4

d

Me

2-FC6 H4

H

97

96–97

5

e

Me

3-FC6 H4

H

98

79–80

6

f

Me

4-FC6 H4

H

95

86–87

7

g

Me

3-BrC6 H4

H

95

119–120

8

h

Me

4-BrC6 H4

H

99

127–128

9

i

Me

2-MeC6 H4

H

96

79–80

10

j

Me

4-MeC6 H4

H

95

85–86

11

k

Me

2, 3-(Cl)2 C6 H3

H

94

94–95

12

l

Me

2, 4-(Cl)2 C6 H3

H

95

103–104

13

m

Me

4-MeOC6 H4

H

94

106–107

14

n

Me

2-MeOC6 H4

H

98

98–99

15

o

Me

2, 5-(MeO)2 C6 H3

H

95

92–93

16

p

Me

3, 4-(MeO)2 C6 H3

H

96

78–79

17

q

Me

C6 H5

Me

95

85–86

18

r

Me

2-ClC6 H4

Me

94

87–88

19

s

Me

4-ClC6 H4

Me

94

89–90

20

t

Me

2-FC6 H4

Me

96

84–85

21

u

Me

3-FC6 H4

Me

95

79–80

22

v

Me

3-BrC6 H4

Me

95

79–80

23

w

Me

2-MeC6 H4

Me

93

85–86

24

x

Me

4-MeC6 H4

Me

95

79–80

25

y

Me

2, 4-(Cl)2 C6 H3

Me

96

103–104

26

z

Me

4-MeOC6 H4

Me

97

120–121

27

aa

Me

2-MeOC6 H4

Me

98

85–86

28

ab

Me

2, 5-(MeO)2 C6 H3

Me

96

80–81

29

ac

Me

3, 4-(MeO)2 C6 H3

Me

96

82–83

30

ad

Me

Naphthyl

Me

95

108–109

31

ae

Et

4-ClC6 H4

H

98

77–78

32

af

Et

2-MeC6 H4

H

94

75–76

33

ag

Et

4-MeOC6 H4

H

96

79–80

34

ah

Et

Naphthyl

H

97

94–95

35

ai

Et

4-ClC6 H4

Me

95

82–83

36

aj

Et

2-MeC6 H4

Me

98

79–80

37

ak

Et

4-MeOC6 H4

Me

94

90–91

38

al

Et

Naphthyl

Me

94

91–92

39

am

Pr

4-ClC6 H4

H

96

81–82

40

an

Pr

2-MeC6 H4

H

98

78–79

123

Mol Divers Table 1 continued Comp 9

R1

41

ao

Pr

4-MeOC6 H4

H

98

76–77

42

ap

Pr

Naphthyl

H

97

95–96

43

aq

Pr

4-ClC6 H4

Me

95

80–81

44

ar

Pr

2-MeC6 H4

Me

98

74–75

45

as

Pr

4-MeOC6 H4

Me

96

78–79

46

at

Pr

Naphthyl

Me

95

92–93

47

au

Benzyl

4-ClC6 H4

H

94

83–84

48

av

Benzyl

2-MeC6 H4

H

98

72–73

49

aw

Benzyl

4-MeOC6 H4

H

97

70–71

50

ax

Benzyl

Naphthyl

H

98

94–95

51

ay

Benzyl

4-ClC6 H4

Me

95

73–74

52

az

Benzyl

2-MeC6 H4

Me

98

76–77

53

aaa

Benzyl

4-MeOC6 H4

Me

96

71–72

54

aab

Benzyl

Naphthyl

Me

98

106–107

a

R2

R3

mp (◦ C)

Entry

Yield (%)a

Quantitative yields were obtained except for the loss during workup

H+ O R2

R3

H O

R3 8

OH R2

H O

O

R2

R2

N R1 7

R3

Michael

O

R2

R2

N R1

R3

N R1

O

14

O-cyclization R2

R2 5

3

R1

4 4a

N 2

1

10a

9

O

5a

R3

6

R3

7 10

R2

9a

9

O

8

O

Elimination -H2O

R1

OH

R3 R3

N 15

R2

H

O

Scheme 5 Plausible mechanism for the formation of 9

1 H, 13 C and the 2D NMR spectra were recorded on a Bruker

(Avance) 300 MHz NMR instrument (1 H–300 MHz, 13 C–75 MHz) using TMS as internal standard and CDCl3 as solvent. Standard Bruker software was used throughout the spectral analysis. Chemical shifts are given in parts per million (δscale), and the coupling constants are given in Hertz. Silica gel-G plates (Merck) were used for TLC analysis with a mixture of n-hexane and ethyl acetate as eluent. All the chemicals were purchased from Sigma-Aldrich and used without any further purification.

123

General procedure for the synthesis of chromeno[3,2-c]pyridines (9a–9aab) A mixture of 3,5-((E)-arylidene)-1-alkylpiperidin-4-one 7 (1.0 mmol) and cyclic 1,3-diketone 8 (1.0 mmol) was dissolved in acetic acid (7–10 mL) in a 50 mL round-bottomed flask and heated to reflux for 12 h continuously. After completion of reaction as indicated by thin-layer chromatography, the mixture was allowed to cool to room temperature, poured into ice-cold water and neutralized with saturated solution

Mol Divers

of sodium bicarbonate. The precipitated solid was filtered, washed with n-hexane (10 mL) and dried under vacuum to obtain pure 9 as white powder.

142.0, 165.6, 197.1. Anal. Calcd. for C26 H23 Cl2 NO2 : C, 69.03; H, 5.12; N, 3.10 %. Found: C, 68.99; H, 5.23; N, 3.46 %.

(E)-4-Benzylidene-2-methyl-10-phenyl-3,4,6,7,8,10hexahydro-1H-chromeno[3,2-c]pyridin-9(2H)-one (9a)

(E)-4-(2-Fluorobenzylidene)-10-(2-fluorophenyl)-2methyl-3,4,6,7,8,10-hexahydro-1H-chromeno[3,2c]pyridin-9(2H)-one (9d)

White solid; Yield: 99 %, Mp.: 76–77 ◦ C; 1 H NMR (300 MHz, CDCl3 ) δH 1.91–1.99 (m, 2H), 2.21 (s, 3H), 2.26–2.32 (m, 2H), 2.55–2.65 (m, 2H), 2.78 (d, J = 16.0 Hz, 1H), 2.96 (d, J = 16.0 Hz, 1H), 3.31 (d, J = 13.6 Hz, 1H), 3.51 (d, J = 13.7 Hz, 1H), 4.22 (s, 1H), 6.92 (s, 1H), 7.13 (dd, J = 10.9, 4.3 Hz, 1H), 7.17 (s, 1H), 7.21 (d, J = 2.8 Hz, 2H), 7.24 (d, J = 1.0 Hz, 2H), 7.27 (d, J = 4.6 Hz, 2H), 7.31 (d, J = 7.4 Hz, 2H); 13 C NMR (75 MHz, CDCl3 ) δC 20.2, 27.4, 36.8, 38.1, 44.7, 54.5, 55.5, 113.7, 115.3, 122.1, 126.5, 126.8, 127.5, 128.1, 128.2, 129.0, 136.4, 140.4, 143.5, 165.4, 196.9. Anal. Calcd. for C26 H25 NO2 : C, 81.43; H, 6.57; N, 3.65 %. Found: C, 81.23; H, 6.40; N, 3.75 %.

White solid; Yield: 97 %, Mp.:96–97 ◦ C; 1 H NMR (300 MHz, CDCl3 ) δH 2.01–2.05 (m, 2H), 2.20 (s, 3H), 2.64–2.73 (m, 2H), 2.77 (s, 1H), 3.00 (d, J = 15.9 Hz, 1H), 3.21 (d, J = 13.6 Hz, 1H), 3.37 (d, J = 13.6 Hz, 1H), 4.51 (s, 1H), 6.97 (s, 1H), 7.03–7.12 (m, 4H), 7.18 (dd, J = 7.2, 5.1 Hz, 4H); 13 C NMR (75 MHz, CDCl3 ) δC 20.1, 27.5, 34.0, 37.0, 44.6, 54.5, 55.2, 114.4, 116.0, 121.3, 125.3, 126.3, 126.5, 127.2, 127.4, 128.4, 128.9, 129.9, 135.5, 135.9, 136.8, 139.9, 142.6, 165.6, 197.2. Anal. Calcd. for C26 H23 F2 NO2 : C, 74.45; H, 5.53; N, 3.34 %. Found: C, 74.56; H, 5.42; N, 3.54 %.

(E)-4-(2-Chlorobenzylidene)-10-(2-chlorophenyl)-2methyl-3,4,6,7,8,10-hexahydro-1H-chromeno[3,2c]pyridin-9(2H)-one (9b)

(E)-4-(3-Fluorobenzylidene)-10-(3-fluorophenyl)-2methyl-3,4,6,7,8,10-hexahydro-1H-chromeno[3,2c]pyridin-9(2H)-one (9e)

White solid; Yield: 98 %, Mp.:87–88 ◦ C; 1 H NMR (300 MHz, CDCl3 ) δH 2.01–2.09 (m, 2H), 2.24 (s, 3H), 2.32–2.39 (m, 2H), 2.66–2.77 (m, 2H), 2.82 (s, 1H), 3.14 (d, J = 16.5 Hz, 1H), 3.22 (d, J = 14.2 Hz, 1H), 3.39 (d, J = 13.7 Hz, 1H), 4.87 (s, 1H), 7.03 (s, 1H), 7.11 (d, J = 7.2 Hz, 1H), 7.16 (d, J = 8.8 Hz, 2H), 7.20 (d, J = 2.3 Hz, 1H), 7.21–7.25 (m, 2H), 7.33 (d, J = 7.7 Hz, 2H), 7.40–7.44 (m, 1H); 13 C NMR (75 MHz, CDCl3 ) δC 20.5, 27.6, 36.9, 44.6, 54.4, 55.0, 119.9, 126.3, 127.3, 127.8, 128.5, 128.6, 129.4, 129.6, 130.0, 130.4, 133.5, 134.1, 133.5, 134.1, 134.7, 139.9, 166.4, 196.9. Anal. Calcd. for C26 H23 Cl2 NO2 : C, 69.03; H, 5.12; N, 3.10 %. Found: C, 68.98; H, 5.23; N, 3.43 %.

White solid; Yield: 98 %, Mp.:79–80 ◦ C; 1 H NMR (300 MHz, CDCl3 ) δH 2.03–2.06 (m, 2H), 2.29 (s, 3H), 2.36–2.38 (m, 2H), 2.55–2.73 (m, 2H), 2.84 (d, J = 15.9 Hz, 1H), 3.02 (d, J = 15.9 Hz, 1H), 3.36 (d, J = 13.8 Hz, 1H), 3.55 (d, J = 13.7 Hz, 1H), 4.29 (s, 1H), 6.89 (s, 1H), 6.98 (dd, J = 20.6, 9.1 Hz, 5H), 7.10 (d, J = 7.7 Hz, 1H), 7.22 (d, J = 7.5 Hz, 1H), 7.33 (d, J = 7.0 Hz, 1H); 13 C NMR (75 MHz, CDCl3 ) δC 20.4, 27.6, 37.0, 38.1, 44.9, 54.6, 55.6, 113.5, 113.8, 114.1, 115.0, 115.2, 115.6, 116.0, 121.5, 124.0, 124.9, 128.6, 129.7, 138.7, 140.5, 146.2, 161.4, 164.3, 165.8, 197.0. Anal. Calcd. for C26 H23 F2 NO2 : C, 74.45; H, 5.53; N, 3.34 %. Found: C, 74.54; H, 5.64; N, 3.56 %.

(E)-4-(4-Chlorobenzylidene)-10-(4-chlorophenyl)-2methyl-3,4,6,7,8,10-hexahydro-1H-chromeno[3,2c]pyridin-9(2H)-one (9c) ◦ C; 1 H

NMR (300 White solid; Yield: 96 %, Mp.:92–93 MHz, CDCl3 ) δH 1.99–2.05 (m, 2H), 2.28 (s, 3H), 2.33– 2.36 (m, 2H), 2.59–2.70 (m, 2H), 2.81 (d, J = 16.1 Hz, 1H), 3.00 (d, J = 16.0 Hz, 1H), 3.36 (d, J = 13.6 Hz, 1H), 3.52 (d, J = 13.7 Hz, 1H), 4.26 (s, 1H), 6.92 (s, 1H), 7.16 (d, J = 8.4 Hz, 2H), 7.24 (s, 4H), 7.34 (d, J = 8.4 Hz, 2H; 13 C NMR (75 MHz, CDCl3 ) δC 20.3, 27.5, 36.8, 37.6, 44.7, 54.5, 55.3, 113.5, 115.2, 121.4, 127.9, 128.4, 128.5, 129.6, 130.3, 132.4, 132.8, 134.8, 140.5,

(E)-4-(4-Fluorobenzylidene)-10-(4-fluorophenyl)-2methyl-3,4,6,7,8,10-hexahydro-1H-chromeno[3,2c]pyridin-9(2H)-one (9f) White solid; Yield: 95 %, Mp.: 86–87 ◦ C; 1 H NMR (300 MHz, CDCl3 ) δH 1.93–2.11 (m, 2H), 2.28 (s, 3H), 2.32– 2.39 (m, 2H), 2.63–2.68 (m, 2H), 2.82 (d, J = 16.0 Hz, 1H), 2.99 (d, J = 16.0 Hz, 1H), 3.36 (d, J = 13.9 Hz, 1H), 3.51 (d, J = 13.6 Hz, 1H), 4.26 (s, 1H), 6.93 (s, 1H), 6.94–7.10 (m, 4H), 7.16–7.26 (m, 3H), 7.27–7.30 (m, 1H); 13 C NMR (75 MHz, CDCl3 ) δC 20.2, 27.4, 36.8, 37.4, 44.8, 54.5, 55.4, 113.7, 114.9, 115.0, 115.1, 115.2, 115.3, 121.3, 127.4, 129.6, 129.7, 130.6, 130.7, 132.3, 132.4, 139.3, 140.4, 162.9, 197.0. Anal. Calcd. for C26 H23 F2 NO2 : C,

123

Mol Divers

74.45; H, 5.53; N, 3.34 %. Found: C, 73.96; H, 5.00; N, 3.78 %.

81.72; H, 7.10; N, 3.40 %. Found: C, 81.24; H, 6.59; N, 3.00 %.

(E)-4-(3-Bromobenzylidene)-10-(3-bromophenyl)-2methyl-3,4,6,7,8,10-hexahydro-1H-chromeno[3,2c]pyridin-9(2H)-one (9g)

(E)-2-Methyl-4-(4-methylbenzylidene)-10-(p-tolyl)3,4,6,7,8,10-hexahydro-1H-chromeno[3,2-c]pyridin-9(2H)one (9j)

White solid; Yield: 95–98 %, Mp.:119–120 ◦ C; 1 H NMR (300 MHz, CDCl3 ) δH 1.99–2.06 (m, 2H), 2.29 (s, 3H), 2.33– 2.38 (m, 2H), 2.60–2.70 (m, 2H), 2.85 (d, J = 16.1 Hz, 1H), 3.05 (d, J = 16.0 Hz, 1H), 3.40 (d, J = 13.8 Hz, 1H), 3.56 (d, J = 14.0 Hz, 1H), 4.25 (s, 1H), 6.94 (s, 1H), 7.13–7.26 (m, 6H), 7.34 (d, J = 8.5 Hz, 2H); 13 C NMR (75 MHz, CDCl3 ) δC 20.3, 27.5, 36.8, 37.6, 44.0, 53.8, 54.7, 113.5, 114.4, 122.2, 126.8, 128.5, 128.6, 129.6, 130.3, 132.5, 133.0, 134.6, 140.4, 141.8, 165.6, 197.2. Anal. Calcd. for C26 H23 Br2 NO2 : C, 57.69; H, 4.28; N, 2.59 %. Found: C, 57.10; H, 3.97; N, 2.00 %.

White solid; Yield: 95 %, Mp.:85–86 ◦ C; 1 H NMR (300 MHz, CDCl3 ) δH 1.97–2.04 (m, 2H), 2.27 (s, 3H), 2.29 (s, 3H), 2.32 (d, J = 5.1 Hz, 2H), 2.36 (s, 3H), 2.64–2.67 (m, 2H), 2.85 (d, J = 16.2 Hz, 1H), 3.01 (d, J = 15.8 Hz, 1H), 3.36 (d, J = 14.0 Hz, 1H), 3.58 (d, J = 13.7 Hz, 1H), 4.23 (s, 1H), 6.94 (s, 1H), 7.07–7.09 (m, 2H), 7.15–7.21 (m, 6H); 13 C NMR (75 MHz, CDCl3 ) δC 20.4, 21.0, 21.2, 27.6, 37.0, 37.8, 44.8, 54.7, 55.6, 114.0, 115.1, 122.2, 126.9, 128.1, 129.0, 129.1, 129.3, 133.7, 136.2, 136.8, 140.5, 140.7, 165.5, 197.2. Anal. Calcd. for C28 H29 NO2 : C, 81.72; H, 7.10; N, 3.40 %. Found: C, 81.26; H, 6.54; N, 3.00 %.

(E)-4-(4-Bromobenzylidene)-10-(4-bromophenyl)-2methyl-3,4,6,7,8,10-hexahydro-1H-chromeno[3,2c]pyridin-9(2H)-one (9h)

(E)-4-(2,3-Dichlorobenzylidene)-10-(2,3-dichlorophenyl)2-methyl-3,4,6,7,8,10-hexahydro-1H-chromeno[3,2c]pyridin-9(2H)-one (9k)

White solid; Yield: 99 %, Mp.:127–128 ◦ C; 1 H NMR (300 MHz, CDCl3 ) υmax (KBr) = 1662, 1626, 1375, 1217 cm−1 ; δH 1.95–2.06 (m, 2H), 2.28 (s, 3H), 2.32–2.37 (m, 2H), 2.60– 2.68 (m, 2H), 2.82 (d, J = 16.5 Hz, 1H), 3.00 (d, J = 16.7 Hz, 1H), 3.35 (d, J = 13.6 Hz, 1H), 3.52 (d, J = 14.1 Hz, 1H), 4.24 (s, 1H), 6.90 (s, 1H), 7.10 (d, J = 8.4 Hz, 2H), 7.19 (d, J = 8.4 Hz, 2H), 7.40 (d, J = 8.3 Hz, 2H), 7.49 (d, J = 8.4 Hz, 2H); 13 C NMR (75 MHz, CDCl3 ) δC 20.3, 27.5, 36.8, 37.7, 44.6, 54.4, 55.2, 113.4, 115.0, 120.6, 121.1, 121.7, 127.7, 130.0, 130.6, 131.4, 131.5, 135.2, 140.5, 142.5, 165.6, 197.1. Anal. Calcd. for C26 H23 Br2 NO2 : C, 57.69; H, 4.28; N, 2.59 %. Found: C, 57.15; H, 3.98; N, 2.05 %; ESI-MS m/z calc [M + H]+ 542.00, found 542.05.

White solid; Yield: 94 %, Mp.: 94–95 ◦ C; 1 H NMR (300 MHz, CDCl3 ) δH 2.02–2.09 (m, 2H), 2.24 (s, 3H), 2.33–2.40 (m, 2H), 2.68–2.73 (m, 2H), 2.79 (s, 1H), 3.07–3.24 (m, 2H), 3.35 (d, J = 13.9 Hz, 1H), 4.93 (s, 1H), 7.00 (s, 1H), 7.06 (d, J = 7.6 Hz, 1H), 7.17 (dd, J = 15.4, 7.4 Hz, 3H), 7.31 (dd, J = 6.8, 2.7 Hz, 1H), 7.40 (d, J = 8.0 Hz, 1H); 13 C NMR (75 MHz, CDCl3 ) δC 27.5, 36.8, 44.6, 54.3, 54.9, 65.9, 112.9, 115.6, 120.1, 126.8, 127.5, 128.2, 128.5, 128.9, 129.1, 129. 2, 131.9, 132.2, 133.1, 133.4, 136.9, 140.0, 143.3, 166.4, 196.8. Anal. Calcd. for C26 H21 Cl4 NO2 : C, 59.91; H, 4.06; N, 2.69 %. Found: C, 59.56; H, 3.55; N, 2.13 %.

(E)-2-Methyl-4-(2-methylbenzylidene)-10-(o-tolyl)3,4,6,7,8,10-hexahydro-1H-chromeno[3,2-c]pyridin-9(2H)one (9i) ◦ C; 1 H

NMR (300 White solid; Yield: 96 %, Mp.:79–80 MHz, CDCl3 ) δH 2.02–2.05 (m, 2H), 2.21 (s, 3H), 2.32 (s, 3H), 2.36 (s, 2H), 2.59 (s, 3H), 2.62–2.71 (m, 2H), 2.75 (d, J = 15.2 Hz, 1H), 3.00 (d, J = 16.0 Hz, 1H), 3.21 (d, J = 13.3 Hz, 1H), 3.37 (d, J = 13.4 Hz, 1H), 4.51 (s, 1H), 6.97 (s, 1H), 7.04–7.12 (m, 3H), 7.12–7.23 (m, 5H); 13 C NMR (75 MHz, CDCl ) 3 δC 19.8, 20.0, 20.4, 27.6, 33.9, 36.9, 44.7, 54.6, 55.3, 114.5, 116.1, 121.3, 125.3, 126.3, 126.5, 127.2, 127.5, 128.4, 129.0, 129.9, 135.5, 135.9, 136.9, 139.9, 142.6, 165.7, 197.2. Anal. Calcd. for C28 H29 NO2 : C,

123

(E)-4-(2,4-Dichlorobenzylidene)-10-(2,4-dichlorophenyl)2-methyl-3,4,6,7,8,10-hexahydro-1H-chromeno[3,2c]pyridin-9(2H)-one (9l) White solid; Yield: 95 %, Mp.:103–104 ◦ C; 1 H NMR (300 MHz, CDCl3 ) δH 2.03–2.08 (m, 2H), 2.25 (s, 3H), 2.32–2.39 (m, 2H), 2.65–2.74 (m, 2H), 2.78 (s, 1H), 3.10 (d, J = 16.1 Hz, 1H), 3.19 (d, J = 14.1 Hz, 1H), 3.35 (d, J = 13.4 Hz, 1H), 4.81 (s, 1H), 6.95 (s, 1H), 7.05–7.24 (m, 4H), 7.33–7.45 (m, 2H); 13 C NMR (75 MHz, CDCl3 ) δC 20.4, 27.5, 34.7, 36.8, 44.6, 54.4, 54.9, 112.7, 115.4, 119.1, 126.7, 127.6, 129.1, 129.2, 129.5, 131.0, 132.9, 133.2, 133.6, 134.2, 134.8, 140.0, 166.5, 196.8. Anal. Calcd. for C26 H21 Cl4 NO2 : C, 59.91; H, 4.06; N, 2.69 %. Found: C, 59.52; H, 3.64; N, 2.18 %.

Mol Divers

(E)-4-(4-Methoxybenzylidene)-10-(4-methoxyphenyl)-2methyl-3,4,6,7,8,10-hexahydro-1H-chromeno[3,2c]pyridin-9(2H)-one (9m)

(E)-4-(3,4-Dimethoxybenzylidene)-10-(3,4dimethoxyphenyl)-2-methyl-3,4,6,7,8,10-hexahydro-1Hchromeno[3,2-c]pyridin-9(2H)-one (9p)

White solid; Yield: 94 %, Mp.:106–107 ◦ C; 1 H NMR (300 MHz, CDCl3 ) δH 1.94–2.05 (m, 2H), 2.28 (s, 3H), 2.31–2.38 (m, 2H), 2.57–2.70 (m, 2H), 2.85 (d, J = 15.9 Hz, 1H), 2.99 (d, J = 15.9 Hz, 1H), 3.38 (d, J = 13.6 Hz, 1H), 3.57 (d, J = 13.7 Hz, 1H), 3.77 (s, 3H), 3.83 (s, 3H), 4.22 (s, 1H), 6.81 (d, J = 8.5 Hz, 2H), 6.93 (dd, J = 15.6, 8.5 Hz, 3H), 7.17-7.24 (m, 4H); 13 C NMR (75 MHz, CDCl3 ) δC 20.3, 27.6, 36.9, 37.3, 44.8, 54.7, 55.1, 55.2, 55.5, 113.7, 114.0, 114.7, 121.8, 126.1, 129.2, 130.4, 132.2, 135.9, 140.5, 158.2, 158.5, 165.4, 197.3. Anal. Calcd. for C28 H29 NO4 : C, 75.82; H, 6.59; N, 3.16 %. Found: C, 75.36; H, 6.06; N, 2.65 %.

White solid; Yield: 96 %, Mp.:78–79 ◦ C; 1 H NMR (300 MHz, CDCl3 ) δH 2.02–2.05 (m, 2H), 2.29 (s, 3H), 2.34– 2.38 (m, 2H), 2.61–2.71 (m, 2H), 2.88 (d, J = 15.7 Hz, 1H), 3.02 (d, J = 16.2 Hz, 1H), 3.41 (d, J = 13.7 Hz, 1H), 3.60 (d, J = 13.8 Hz, 1H), 3.84 (s, 3H), 3.89 (d, J = 2.1 Hz, 6H), 3.91 (s, 3H), 4.22 (s, 1H), 6.79 (d, J = 3.5 Hz, 2H), 6.82 (s, 2H), 6.87 (d, J = 2.5 Hz, 2H), 6.92 (s, 1H); 13 C NMR (75 MHz, CDCl3 ) δC 20.4, 27.6, 37.0, 37.8, 44.8, 54.8, 55.4, 55.6, 55.7, 55.8, 55.9, 56.0, 111.2, 111.5, 112.3, 112.8, 114.1, 114.9, 120.2, 121.8, 122.1, 126.6, 129.6, 136.6, 140.6, 147.9, 148.4, 148.8, 148.9, 165.4, 197.1. Anal. Calcd. for C30 H33 NO6 : C, 71.55; H, 6.61; N, 2.78 %. Found: C, 71.05; H, 6.14; N, 2.25 %.

(E)-4-(2-Methoxybenzylidene)-10-(2-methoxyphenyl)-2methyl-3,4,6,7,8,10-hexahydro-1H-chromeno[3,2c]pyridin-9(2H)-one (9n) White solid; Yield: 98 %, Mp.:98–99 ◦ C; 1 H NMR (300 MHz, CDCl3 ) δH 2.03–2.06 (m, 2H), 2.22 (s, 3H), 2.32–2.37 (m, 2H), 2.68–2.72 (m, 2H), 2.81 (d, J = 16.0 Hz, 1H), 3.11 (d, J = 16.1 Hz, 1H), 3.22 (d, J = 13.6 Hz, 1H), 3.44 (d, J = 13.7 Hz, 1H), 3.84 (s, 3H), 3.91 (s, 3H), 4.79 (s, 1H), 6.85–6.95 (m, 4H), 7.00 (s, 1H), 7.07–7.14(m, 4H); 13 C NMR (75 MHz, CDCl3 ) δC 20.6, 27.7, 30.7, 37.0, 44.5, 54.8, 55.3, 55.4, 56.1, 110.6, 111.3, 113.4, 115.4, 117.8, 120.0, 121.1, 125.7, 127.5, 127.6, 128.4, 128.9, 130.1, 132.8, 140.0, 157.1, 157.3, 166.5, 196.9. Anal. Calcd. for C28 H29 NO4 : C, 75.82; H, 6.59; N, 3.16 %. Found: C, 75.38; H, 6.14; N, 2.68 %.

(E)-4-(2,5-Dimethoxybenzylidene)-10-(2,5dimethoxyphenyl)-2-methyl-3,4,6,7,8,10-hexahydro-1Hchromeno[3,2-c]pyridin-9(2H)-one (9o) White solid; Yield: 95 %, Mp.:92–93 ◦ C; 1 H NMR (300 MHz, CDCl3 ) δH 2.05–2.09 (m, 2H), 2.24 (s, 3H), 2.33–2.36 (m, 2H), 2.68–2.71 (m, 2H), 2.82 (d, J = 16.3 Hz, 1H), 3.12 (d, J = 16.7 Hz, 1H), 3.23 (d, J = 13.3 Hz, 1H), 3.46 (d, J = 13.6 Hz, 1H), 3.73 (s, 3H), 3.77 (s, 3H), 3.80 (s, 3H), 3.88 (s, 3H), 4.76 (s, 1H), 6.65 (d, J = 2.7 Hz, 2H), 6.68 (d, J = 2.5 Hz, 2H), 6.80 (d, J = 3.1 Hz, 2H), 6.96 (s, 1H); 13 C NMR (75 MHz, CDCl3 ) δC 20.5, 27.5, 30.8, 37.0, 44.6, 54.7, 55.2, 55.5, 55.7, 56.1, 57.0, 111.1, 111.6, 112.6, 112.7, 113.1, 115.5, 115.7, 116.2, 117.8, 126.5, 127.9, 134.3, 139.8, 151.5, 151.7, 153.0, 154.0, 166.7, 197.1. Anal. Calcd. for C30 H33 NO6 : C, 71.55; H, 6.61; N, 2.78 %. Found: C, 71.04; H, 6.16; N, 2.27 %.

(E)-4-Benzylidene-2,7,7-trimethyl-10-phenyl-3,4,6,7,8,10hexahydro-1H-chromeno[3,2-c]pyridin-9(2H)-one (9q) White solid; Yield: 95 %, Mp.:85–86 ◦ C; 1 H NMR (300 MHz, CDCl3 ) δH 1.12 (s, 3H), 1.03 (s, 3H), 2.22 (d, J = 7.0 Hz, 2H), 2.27 (s, 3H), 2.55 (s, 2H), 2.83 (d, J = 16.0 Hz, 1H), 3.05 (d, J = 16.2 Hz, 1H), 3.36 (d, J = 13.7 Hz, 1H), 3.61 (d, J = 13.6 Hz, 1H), 4.25 (s, 1H), 6.98 (s, 1H), 7.19 (dd, J = 5.8, 3.0 Hz, 1H), 7.22 (s, 1H), 7.25 (s, 1H), 7.27–7.30 (m, 4H), 7.36 (d, J = 7.6 Hz, 2H), 7.40 (d, J = 7.2 Hz, 1H); 13 C NMR (75 MHz, CDCl3 ) δC 27.5, 29.0, 32.1, 38.3, 41.2, 44.4, 50.7, 54.3, 55.3, 112.4, 115.0, 122.6, 126.7, 127.0, 127.2, 128.1, 128.2, 128.3, 129.1, 136.4, 143.5, 163.8, 197.0. Anal. Calcd. for C28 H29 NO2 : C, 81.72; H, 7.10; N, 3.40 %. Found: C, 81.28; H, 6.64; N, 3.00 %.

(E)-4-(2-Chlorobenzylidene)-10-(2-chlorophenyl)-2,7,7trimethyl-3,4,6,7,8,10-hexahydro-1H-chromeno[3,2c]pyridin-9(2H)-one (9r) White solid; Yield: 94 %, Mp.:87–88 ◦ C; 1 H NMR (300 MHz, CDCl3 ) δH 1.09 (s, 3H), 1.14 (s, 3H), 2.07–2.22 (m, 2H), 2.25 (s, 3H), 2.58 (s, 2H), 2.78 (d, J = 16.2 Hz, 1H), 3.19 (dd, J = 19.4, 15.3 Hz, 2H), 3.42 (d, J = 13.6 Hz, 1H), 4.87 (s, 1H), 7.03 (s, 1H), 7.11–7.25 (m, 5H), 7.37 (d, J = 14.3, 7.3, 4.1 Hz, 3H); 13 C NMR (75 MHz, CDCl3 ) δC 27.6, 29.1, 32.1, 32.1, 41.3, 44.4, 50.7, 54.4, 55.0, 111.8, 115.4, 120.0, 126.3, 127.2, 127.9, 128.5, 128.6, 129.5, 129.6, 130.1, 130.4, 133.5, 134.1, 134.8, 140.2, 164.6, 164.7, 196.6. Anal. Calcd. for C28 H27 Cl2 NO2 : C, 70.00; H, 5.66; N, 2.92 %. Found: C, 69.58; H, 5.19; N, 2.57 %.

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Mol Divers

(E)-4-(4-Chlorobenzylidene)-10-(4-chlorophenyl)-2,7,7trimethyl-3,4,6,7,8,10-hexahydro-1H-chromeno[3,2c]pyridin-9(2H)-one (9s)

(E)-4-(3-Bromobenzylidene)-10-(3-bromophenyl)-2,7,7trimethyl-3,4,6,7,8,10-hexahydro-1H-chromeno[3,2c]pyridin-9(2H)-one (9v)

White solid; Yield: 94 %, Mp.:89–90 ◦ C; 1 H NMR (300 MHz, CDCl3 ) δH 1.02 (s, 3H), 1.12 (s, 3H), 2.22 (d, J = 8.1 Hz, 2H), 2.28 (s, 3H), 2.53 (s, 2H), 2.80 (d, J = 15.9 Hz, 1H), 3.02 (d, J = 16.3 Hz, 1H), 3.34 (d, J = 13.4 Hz, 1H), 3.54 (d, J = 13.7 Hz, 1H), 4.23 (s, 1H), 6.91 (s, 1H), 7.16 (d, J = 8.5 Hz, 2H), 7.27 (s, 2H), 7.31–7.43 (m, 4H); 13 C NMR (75 MHz, CDCl3 ) δC 27.4, 29.0, 32.1, 37.7, 41.2, 44.5, 50.7, 54.3, 55.1, 112.2, 115.0, 121.7, 127.6, 128.5, 128.6, 128.8, 129.5, 130.3, 131.5, 132.5, 132.9, 134.8, 140.4, 141.9, 163.9, 197.0. Anal. Calcd. for C28 H27 Cl2 NO2 : C, 70.00; H, 5.66; N, 2.92 %. Found: C, 69.56; H, 5.04; N, 2.49 %.

White solid; Yield: 95 %, Mp.:79–80 ◦ C; 1 H NMR (300 MHz, CDCl3 ) δH 1.05 (s, 3H), 1.12 (s, 3H), 2.23 (d, J = 4.3 Hz, 2H), 2.30 (s, 3H), 2.55 (d, J = 5.6 Hz, 2H), 2.82 (d, J = 16.1 Hz, 1H), 3.04 (d, J = 16.1 Hz, 1H), 3.34 (d, J = 13.6 Hz, 1H), 3.56 (d, J = 13.8 Hz, 1H), 4.22 (s, 1H), 6.91 (s, 1H), 7.20 (dd, J = 19.4, 7.7 Hz, 4H), 7.31– 7.41 (m, 4H); 13 C NMR (75 MHz, CDCl3 ) δC 27.5, 28.9, 32.1, 38.1, 41.2, 44.5, 50.6, 54.1, 55.1, 111.9, 115.1, 121.5, 122.3, 122.6, 126.9, 127.5, 128.2, 129.8, 129.9, 129.9, 130.0, 131.0, 131.9, 138.4, 140.3, 145.6, 164.0, 196.8. Anal. Calcd. for C28 H27 Br2 NO2 : C, 59.07; H, 4.78; N, 2.46 %. Found: C, 58.57; H, 4.28; N, 2.02 %.

(E)-4-(2-Fluorobenzylidene)-10-(2-fluorophenyl)-2,7,7trimethyl-3,4,6,7,8,10-hexahydro-1H-chromeno[3,2c]pyridin-9(2H)-one (9t)

(E)-2,7,7-Trimethyl-4-(2-methylbenzylidene)-10-(o-tolyl)3,4,6,7,8,10-hexahydro-1H-chromeno[3,2-c]pyridin-9(2H)one (9w)

White solid; Yield: 96 %, Mp.:84–85 ◦ C; 1 H NMR (300 MHz, CDCl3 ) δH 1.05 (s, 3H), 1.12 (s, 3H), 2.18 (d, J = 3.4 Hz, 2H), 2.21 (s, 3H), 2.55 (d, J = 3.3 Hz, 2H), 2.80 (d, J = 19.5 Hz, 1H), 3.02 (d, J = 15.9 Hz, 1H), 3.19 (d, J = 13.7 Hz, 1H), 3.39 (d, J = 13.4 Hz, 1H), 4.51 (s, 1H), 6.96 (s, 1H), 7.05–7.09 (m, 3H), 7.16 (d, J = 6.8 Hz, 3H), 7.18–7.21 (m, 2H); 13 C NMR (75 MHz, CDCl3 ) δC 20.0, 27.6, 29.1, 32.2, 41.3, 44.7, 50.8, 54.7, 55.4, 121.4, 125.4, 126.4, 126.5, 127.3, 127.6, 129.0, 130.0, 130.4, 133.2, 135.6, 136.0, 136.1, 137.0, 138.3, 140.1, 164.0, 197.2. Anal. Calcd. for C28 H27 F2 NO2 : C, 75.15; H, 6.08; N, 3.13 %. Found: C, 74.74; H, 5.68; N, 2.63 %.

White solid; Yield: 93 %, Mp.:85–86 ◦ C; 1 H NMR (300 MHz, CDCl3 ) δH 1.05 (s, 3H), 1.13 (s, 3H), 2.19 (s, 1H), 2.21 (s, 3H), 2.33 (s, 3H), 2.37 (s, 1H), 2.56 (s, 2H), 2.59 (s, 3H), 2.81 (d, J = 17.0 Hz, 1H), 3.04 (d, J = 15.9 Hz, 1H), 3.20 (d, J = 13.6 Hz, 1H), 3.40 (d, J = 13.6 Hz, 1H), 4.51 (s, 1H), 6.97 (s, 1H), 7.04–7.10 (m, 3H), 7.15 (t, J = 5.6 Hz, 3H), 7.20 (d, J = 2.3 Hz, 2H); 13 C NMR (75 MHz, CDCl3 ) δC 19.8, 20.0, 27.5, 29.0, 32.1, 41.2, 44.4, 50.7, 54.4, 55.1, 113.1, 115.8, 121.5, 125.3, 126.3, 126.4, 127.2, 128.2, 128.9, 129.9, 135.4, 135.8, 136.8, 139.9, 142.5, 163.9, 197.1. Anal. Calcd. for C30 H33 NO2 : C, 81.97; H, 7.57; N, 3.19 %. Found: C, 81.54; H, 7.07; N, 2.79 %.

(E)-4-(3-Fluorobenzylidene)-10-(3-fluorophenyl)-2,7,7trimethyl-3,4,6,7,8,10-hexahydro-1H-chromeno[3,2c]pyridin-9(2H)-one (9u)

(E)-2,7,7-Trimethyl-4-(4-methylbenzylidene)-10-(p-tolyl)3,4,6,7,8,10-hexahydro-1H-chromeno[3,2-c]pyridin-9(2H)one (9x)

White solid; Yield: 95 %, Mp.:79–80 ◦ C; 1 H NMR (300 MHz, CDCl3 ) δH 1.05 (s, 3H), 1.12 (s, 3H), 2.23 (d, J = 5.8 Hz, 2H), 2.29 (s, 3H), 2.51 (dd, J = 22.1, 3.2 Hz, 2H), 2.83 (d, J = 16.1 Hz, 1H), 3.05 (d, J = 16.1 Hz, 1H), 3.36 (d, J = 14.6 Hz, 1H), 3.58 (d, J = 13.8 Hz, 1H), 4.26 (s, 1H), 6.95 (dd, J = 7.1, 4.6 Hz, 3H), 7.00 (s, 1H), 7.07–7.24 (m, 3H), 7.28–7.38 (m, 2H); 13 C NMR (75 MHz, CDCl3 ) δC 27.3, 28.8, 32.0, 38.0, 41.0, 44.3, 50.5, 54.1, 55.0, 111.9, 113.5, 113.7, 114.0, 114.6, 114.9, 115.0, 115.4, 115.7, 121.5, 123.7, 124.7, 127.9, 129.4, 138.3, 140.2, 145.8, 163.4, 196.8. Anal. Calcd. for C28 H27 F2 NO2 : C, 75.15; H, 6.08; N, 3.13 %. Found: C, 74.67; H, 5.58; N, 2.56 %.

White solid; Yield: 95 %, Mp.:79–80 ◦ C; 1 H NMR (300 MHz, CDCl3 ) δH 1.03 (s, 3H), 1.10 (d, J = 3.6 Hz, 3H), 2.21 (d, J = 6.6 Hz, 2H), 2.27 (s, 3H), 2.29 (s, 3H), 2.36 (s, 3H), 2.54 (s, 2H), 2.83 (d, J = 16.0 Hz, 1H), 3.03 (d, J = 15.9 Hz, 1H), 3.33 (d, J = 13.7 Hz, 1H), 3.61 (d, J = 13.7 Hz, 1H), 4.21 (s, 1H), 6.93 (s, 1H), 7.08 (d, J = 8.0 Hz, 2H), 7.15 (d, J = 5.6 Hz, 4H), 7.19 (s, 1H), 7.31 (d, J = 8.2 Hz, 1H); 13 C NMR (75 MHz, CDCl3 ) δC 21.0, 21.1, 27.5, 29.0, 32.1, 37.9, 41.2, 44.7, 50.8, 54.6, 55.5, 112.6, 115.0, 122.2, 126.9, 128.0, 128.9, 129.0, 129.2, 130.4, 133.6, 136.1, 136.7, 140.3, 140.6, 163.8, 197.0. Anal. Calcd. for C30 H33 NO2 : C, 81.97; H, 7.57; N, 3.19 %. Found: C, 81.57; H, 7.07; N, 2.69 %.

123

Mol Divers

(E)-4-(2,4-Dichlorobenzylidene)-10-(2,4-dichlorophenyl)2,7,7-trimethyl-3,4,6,7,8,10-hexahydro-1H-chromeno[3,2c]pyridin-9(2H)-one (9y)

(E)-4-(2,5-Dimethoxybenzylidene)-10-(2,5dimethoxyphenyl)-2,7,7-trimethyl-3,4,6,7,8,10-hexahydro1H-chromeno[3,2-c]pyridin-9(2H)-one (9ab)

White solid; Yield: 96 %, Mp.:103–104 ◦ C; 1 H NMR (300 MHz, CDCl3 ) δH 1.08 (s, 3H), 1.13 (s, 3H), 2.13–2.21 (m, 2H), 2.26 (s, 3H), 2.57 (s, 2H), 2.75 (d, J = 16.1 Hz, 1H), 3.15 (dd, J = 22.2, 15.0 Hz, 2H), 3.35 (s, 1H), 4.81 (s, 1H), 6.95 (s, 1H), 7.06–7.23 (m, 4H), 7.34–7.45 (m, 2H); 13 C NMR (75 MHz, CDCl3 ) δC 27. 7, 29.1, 32.2, 34.9, 41.3, 44.7, 50.7, 54.5, 55.0, 111.5, 115.4, 119.1, 126.7, 127.6, 129.2, 129.3, 129.5, 129.9, 130.9, 131.1, 133.0, 133.3, 133.7, 134.2, 134.9, 140.3, 164.7, 196.6. Anal. Calcd. for C28 H25 Cl4 NO2 : C, 61.22; H, 4.59; N, 2.55 %. Found: C, 60.82; H, 4.09; N, 2.05 %.

White solid; Yield: 96 %, Mp.:80–81 ◦ C; 1 H NMR (300 MHz, CDCl3 ) δH 1.11 (s, 3H), 1.13 (s, 3H), 2.22 (d, J = 5.5 Hz, 2H), 2.24 (s, 3H), 2.57 (s, 2H), 2.84 (d, J = 16.4 Hz, 1H), 3.17 (d, J = 16.4 Hz, 1H), 3.27 (d, J = 14.5 Hz, 1H), 3.51 (d, J = 13.8 Hz, 1H), 3.71 (s, 3H), 3.77 (s, 3H), 3.80 (s, 3H), 3.87 (s, 3H), 4.74 (s, 1H), 6.65–6.70 (m, 3H), 6.81 (dd, J = 6.3, 3.4 Hz, 3H), 6.98 (s, 1H); 13 C NMR (75 MHz, CDCl3 ) δC 27.6, 29.1, 30.8, 32.0, 41.2, 43.9, 50.7, 54.2, 54.6, 55.5, 55.6, 56.0, 56.9, 111.6, 111.7, 111.7, 112.6, 112.9, 114.7, 115.3, 116.1, 118.3, 126.2, 127.1, 133.8, 139.8, 151.4, 151.6, 152.9, 154.0, 164.8, 197.0. Anal. Calcd. for C32 H37 NO6 : C, 72.29; H, 7.01; N, 2.63 %. Found: C, 71.80; H, 6.58; N, 2.14 %.

(E)-4-(4-Methoxybenzylidene)-10-(4-methoxyphenyl)2,7,7-trimethyl-3,4,6,7,8,10-hexahydro-1H-chromeno[3,2c]pyridin-9(2H)-one (9z) White solid; Yield: 97 %, Mp.:120–121 ◦ C; 1 H NMR (300 MHz, CDCl3 ) δH 1.03 (s, 3H), 1.11 (s, 3H), 2.21 (d, J = 6.2 Hz, 2H), 2.28 (s, 3H), 2.51 (d, J = 12.3 Hz, 2H), 2.83 (d, J = 15.8 Hz, 1H), 3.01 (d, J = 15.8 Hz, 1H), 3.35 (d, J = 13.6 Hz, 1H), 3.59 (d, J = 13.5 Hz, 1H), 3.76 (s, 3H), 3.83 (s, 3H), 4.19 (s, 1H), 6.81 (d, J = 8.5 Hz, 2H), 6.86–6.93 (m, 3H), 7.19 (t, J = 8.6 Hz, 4H); 13 C NMR (75 MHz, CDCl3 ) δC 27.5, 29.0, 32.0, 37.4, 41.2, 44.7, 50.7, 54.7, 55.0, 55.1, 55.4, 112.6, 113.3, 113.7, 114.0, 114.6, 121.8, 126.0, 129.0, 130.3, 132.2, 135.8, 140.4, 158.2, 158.5, 163.7,197.1. Anal. Calcd. for C30 H33 NO4 : C, 76.41; H, 7.05; N, 2.97 %. Found: C, 75.94; H, 6.55; N, 2.58 %. (E)-4-(2-Methoxybenzylidene)-10-(2-methoxyphenyl)2,7,7-trimethyl-3,4,6,7,8,10-hexahydro-1H-chromeno[3,2c]pyridin-9(2H)-one (9aa) ◦ C; 1 H

NMR (300 White solid; Yield: 98 %, Mp.:85–86 MHz, CDCl3 ) δH 1.09 (s, 2H), 1.12 (s, 3H), 2.13–2.20 (m, 2H), 2.22 (s, 3H), 2.57 (s, 2H), 2.79 (d, J = 16.1 Hz, 1H), 3.11 (d, J = 16.2 Hz, 1H), 3.22 (d, J = 13.6 Hz, 1H), 3.45 (d, J = 13.7 Hz, 1H), 3.85 (s, 3H), 3.90 (s, 3H), 4.78 (s, 1H), 6.85–6.97 (m, 5H), 7.00 (s, 1H), 7.07–7.18 (m, 3H); 13 C NMR (75 MHz, CDCl3 ) δC 27.6, 28.3, 29.2, 30.9, 32.1, 41.5, 44.6, 51.0, 54.9, 55.4, 56.1, 110.7, 111.4, 112.2, 115.4, 117.8, 120.1, 121.0, 125.8, 127.6, 127.7, 128.5, 129.1, 130.2, 132.7, 140.2, 157.2, 157.4, 164.8, 196.8. Anal. Calcd. for C30 H33 NO4 : C, 76.41; H, 7.05; N, 2.97 %. Found: C, 76.01; H, 6.65; N, 2.48 %.

(E)-4-(3,4-Dimethoxybenzylidene)-10-(3,4dimethoxyphenyl)-2,7,7-trimethyl-3,4,6,7,8,10-hexahydro1H-chromeno[3,2-c]pyridin-9(2H)-one (9ac) White solid; Yield: 96 %, Mp.:82–83 ◦ C; 1 H NMR (300 MHz, CDCl3 ) δH 1.01 (s, 3H), 1.11 (s, 3H), 2.22 (d, J = 4.7 Hz, 2H), 2.29 (s, 2H), 2.48 (d, J = 8.5 Hz, 3H), 2.87 (d, J = 16.6 Hz, 1H), 3.10 (d, J = 39.4 Hz, 1H), 3.36 (d, J = 33.2 Hz, 1H), 3.65 (d, J = 20.2 Hz, 1H), 3.80 (s, 3H), 3.86 (s, 3H), 3.92 (s, 3H), 3.94 (s, 3H), 4.70 (s, 1H), 6.72– 6.80 (m, 2H), 6.91 (s, 1H), 6.95 (d, J = 3.7 Hz, 2H), 7.02 (d, J = 8.2 Hz, 2H); 13 C NMR (75 MHz, CDCl3 ) δC 27.7, 29.2, 30.9, 32.1, 41.3, 44.0, 50.8, 54.3, 54.7, 55.6, 55.7, 56.1, 57.0, 111.7, 111.9, 112.7, 113.0, 114.8, 115.4, 116.2, 118.5, 126.3, 127.2, 133.9, 139.9, 151.5, 151.7, 153.0, 154.1, 164.9,197.0. Anal. Calcd. for C32 H37 NO6 : C, 72.29; H, 7.01; N, 2.63 %. Found: C, 71.83; H, 6.49; N, 2.17 %.

(E)-2,7,7-Trimethyl-10-(naphthalen-1-yl)-4-(naphthalen1-ylmethylene)-3,4,6,7,8,10-hexahydro-1H-chromeno[3,2c]pyridin-9(2H)-one (9ad) White solid; Yield: 95 %, Mp.:108–109 ◦ C; 1 H NMR (300 MHz, CDCl3 ) δH 1.08 (s, 3H), 1.16 (s, 3H), 2.09 (s, 3H), 2.16–2.25 (m, 2H), 2.55 (d, J = 26.1 Hz, 1H), 2.66 (s, 2H), 3.13 (dd, J = 24.2, 14.5 Hz, 2H), 3.40 (d, J = 13.7 Hz, 1H), 3.66 (s, 1H), 7.45–7.50 (m, 4H), 7.53 (d, J = 4.0 Hz, 2H), 7.56 (dd, J = 6.9, 2.7 Hz, 2H), 7.70–7.80 (m, 2H), 7.85– 7.90 (m, 2H), 8.02–8.12 (m, 2H), 8.52 (s, 1H); 13 C NMR (75 MHz, CDCl3 ) δC 27.7, 29.1, 32.2, 41.4, 44.5, 50.7, 54.8, 55.6, 57.0, 120.5, 123.4, 124.8, 125.0, 125.1, 125.2, 125.5, 125.7, 126.0, 126.3, 126.6, 126.7, 126.9, 127.8, 128.4, 128.5,

123

Mol Divers

128.7, 129.0, 129.4, 131.9, 133.5, 133.6, 135.4, 140.2, 164.1, 197.1. Anal. Calcd. for C36 H33 NO2 : C, 84.51; H, 6.50; N, 2.74 %. Found: C, 84.01; H, 6.00; N, 2.25 %. (E)-4-(4-Chlorobenzylidene)-10-(4-chlorophenyl)-2-ethyl3,4,6,7,8,10-hexahydro-1H-chromeno[3,2-c]pyridin-9(2H)one (9ae) ◦ C; 1 H

White solid; Yield: 98 %, Mp.:77–78 NMR (300 MHz, CDCl3 ) δH 0.97 (t, J = 7.2 Hz, 3H), 2.02 (dd, J = 11.3, 5.4 Hz, 2H), 2.35 (dd, J = 10.6, 5.7 Hz, 2H), 2.39–2.47 (m, 2H), 2.59–2.70 (m, 2H), 2.82 (d, J = 15.8 Hz, 1H), 3.07 (d, J = 16.0 Hz, 1H), 3.33 (d, J = 13.2 Hz, 1H), 3.63 (d, J = 13.9 Hz, 1H), 4.26 (s, 1H), 6.91 (s, 1H), 7.16 (d, J = 8.4 Hz, 2H), 7.24 (s, 4H), 7.33 (d, J = 8.4 Hz, 2H); 13 C NMR (75 MHz, CDCl3 ) δC 12.2, 20.3, 27.5, 36.9, 37.8, 50.8, 52.3, 53.0, 113.6, 115.3, 121.5, 128.0, 128.5, 128.5, 128.5, 129.6, 130.3, 132.5, 132.8, 135.0, 140.8, 142.1, 165.7, 197.1. Anal. Calcd. For C27 H25 Cl2 NO2 : C, 69.53; H, 5.40; N, 3.00 %. Found: C, 69.03; H, 4.98; N, 2.57 %. (E)-2-Ethyl-4-(2-methylbenzylidene)-10-(o-tolyl)3,4,6,7,8,10-hexahydro-1H-chromeno[3,2-c]pyridin-9(2H)one (9af) White solid; Yield: 94 %, Mp.:75–76 ◦ C; 1 H NMR (300 MHz, CDCl3 ) δH 0.90 (t, J = 7.2 Hz, 3H), 2.02 (d, J = 5.8 Hz, 2H), 2.34 (d, J = 10.9 Hz, 6H), 2.59 (s, 4H), 2.72 (d, J = 6.4 Hz, 2H), 2.78 (s, 1H), 3.15 (dd, J = 25.6, 14.7 Hz, 2H), 3.50 (d, J = 13.5 Hz, 1H), 4.52 (s, 1H), 6.98 (s, 1H), 7.09 (d, J = 6.8 Hz, 3H), 7.13–7.22 (m, 5H); 13 C NMR (75 MHz, CDCl3 ) δC 12.2, 19.9, 20.0, 20.4, 27.6, 34.0, 37.0, 50.5, 52.4, 52.8, 114.5, 116.0, 121.4, 125.4, 126.3, 126.5, 127.2, 127.4, 128.4, 128.9, 129.9, 135.5, 135.9, 136.9, 140.1, 142.7, 165.7, 197.2. Anal. Calcd. for C29 H31 NO2 : C, 81.85; H, 7.34; N, 3.29 %. Found: C, 81.36; H, 6.87; N, 2.84 %. (E)-2-Ethyl-4-(4-methoxybenzylidene)-10-(4methoxyphenyl)-3,4,6,7,8,10-hexahydro-1H-chromeno[3,2c]pyridin-9(2H)-one (9ag) White solid; Yield: 96 %, Mp.:79–80 ◦ C; 1 H NMR (300 MHz, CDCl3 ) δH 0.96 (t, J = 7.2 Hz, 3H), 2.01 (d, J = 6.3 Hz, 2H), 2.39 (ddd, J = 23.4, 9.5, 4.3 Hz, 4H), 2.58–2.69 (m, 2H), 2.87 (d, J = 15.9 Hz, 1H), 3.10 (d, J = 15.9 Hz, 1H), 3.37 (d, J = 14.1 Hz, 1H), 3.71 (d, J = 13.6 Hz, 1H), 3.77 (s, 3H), 3.83 (s, 3H), 4.22 (s, 1H), 6.81 (d, J = 8.6 Hz, 2H), 6.90 (d, J = 8.7 Hz, 3H), 7.17 (s, 1H), 7.21 (d, J = 3.1 Hz, 2H), 7.24 (s, 1H); 13 C NMR (75 MHz, CDCl3 ) δC 12.2, 20.4, 27.6, 37.0, 37.5, 50.6, 52.4, 53.1, 55.2, 55.2, 113.8, 114.2, 114.7, 122.1, 126.0, 129.2, 130.4, 136.1, 140.8, 158.4, 158.7, 165.4, 197.2. Anal. Calcd. for C29 H31 NO4 : C,

123

76.12; H, 6.83; N, 3.06 %. Found: C, 75.73; H, 6.38; N, 2.65 %. (E)-2-Ethyl-10-(naphthalen-1-yl)-4-(naphthalen-1ylmethylene)-3,4,6,7,8,10-hexahydro-1H-chromeno[3,2c]pyridin-9(2H)-one (9ah) White solid; Yield: 97 %, Mp.:94–95 ◦ C; 1 H NMR (300 MHz, CDCl3 ) υmax (KBr) = 1664, 1626, 1375, 1217 cm−1 ; δH 0.76 (t, J = 7.1 Hz, 3H), 2.09 (d, J = 5.6 Hz, 2H), 2.24 (dd, J = 7.2, 2.4 Hz, 2H), 2.32–2.39 (m, 2H), 2.65 (d, J = 16.5 Hz, 1H), 2.81 (dd, J = 20.2, 14.8 Hz, 2H), 3.18 (dd, J = 14.9, 7.5 Hz, 2H), 3.51 (d, J = 13.7 Hz, 1H), 5.19 (s, 1H), 7.41–7.46 (m, 1H), 7.46–7.50 (m, 3H), 7.53 (dd, J = 6.7, 2.9 Hz, 2H), 7.56–7.63 (m, 2H), 7.73 (d, J = 7.3 Hz, 1H), 7.77–7.85 (m, 2H), 7.85–7.90 (m, 2H), 8.06 (d, J = 8.6 Hz, 1H), 8.53 (s, 1H); 13 C NMR (75 MHz, CDCl3 ) δC 11.8, 20.3, 27.6, 36.8, 50.2, 52.3, 53.0, 114.5, 116.4, 120.5, 123.3, 124.7, 125.0, 125.0, 125.4, 125.6, 125.8, 125.9, 126.0, 126.2, 126.5, 127.3, 127.7, 128.3, 128.6, 131.6, 131.8, 133.4, 135.4, 140.1, 165.8, 197.1. Anal. Calcd. for C35 H31 NO2 : C, 84.48; H, 6.28; N, 2.81 %. Found: C, 84.00; H, 5.87; N, 2.38 %; ESI-MS m/z calc [M + H]+ 498.24, found 498.31. (E)-4-(4-Chlorobenzylidene)-10-(4-chlorophenyl)-2-ethyl7,7-dimethyl-3,4,6,7,8,10-hexahydro-1H-chromeno[3,2c]pyridin-9(2H)-one (9ai) White solid; Yield: 95 %, Mp.:82–83 ◦ C; 1 H NMR (300 MHz, CDCl3 ) δH 0.97 (t, J = 6.1 Hz, 3H), 1.03 (s, 3H), 1.11 (s, 3H), 2.21 (d, J = 7.1 Hz, 2H), 2.40–2.47 (m, 2H), 2.53 (d, J = 3.6 Hz, 2H), 2.79 (d, J = 16.1 Hz, 1H), 3.10 (d, J = 16.3 Hz, 1H), 3.29 (d, J = 13.9 Hz, 1H), 3.66 (d, J = 13.6 Hz, 1H), 4.24 (s, 1H), 6.91 (s, 1H), 7.16 (d, J = 8.4 Hz, 2H), 7.27 (s, 3H), 7.34 (d, J = 8.4 Hz, 3H); 13 C NMR (75 MHz, CDCl3 ) δC 12.2,27.5, 28.9, 32.2, 38.0, 41.2, 50.8, 52.2, 53.0, 112.2, 115.1, 121.6, 127.9, 128.5, 128.5, 128.8, 129.5, 130.3, 131.5, 132.4, 132.9, 134.8, 140.7, 142.0, 163.9, 197.0. Anal. Calcd. for C29 H29 Cl2 NO2 : C, 70.44; H, 5.91; N, 2.83 %. Found: C, 69.98; H, 5.57; N, 2.53 %. (E)-2-Ethyl-7,7-dimethyl-4-(2-methylbenzylidene)-10-(otolyl)-3,4,6,7,8,10-hexahydro-1H-chromeno[3,2-c]pyridin9(2H)-one (9aj) White solid; Yield: 98 %, Mp.:79–80 ◦ C; 1 H NMR (300 MHz, CDCl3 ) δH 0.91 (t, J = 7.2 Hz, 3H), 1.06 (s, 3H), 1.12 (s, 3H), 2.20 (d, J = 7.7 Hz, 2H), 2.33 (s, 3H), 2.37 (t, J = 3.6 Hz, 2H), 2.55 (d, J = 6.9 Hz, 2H), 2.59 (s, 3H), 2.74 (d, J = 16.0 Hz, 1H), 3.15 (dd, J = 14.5, 9.4 Hz, 2H), 3.52 (d, J = 13.6 Hz, 1H), 4.51 (s, 1H), 6.97 (s, 1H), 7.05–7.10 (m, 3H), 7.12–7.18 (m, 4H), 7.18–7.21 (m,

Mol Divers

2H); 13 C NMR (75 MHz, CDCl3 ) δC 12.1, 19.9, 20.0, 27.6, 29.0, 32.2, 41.3, 50.6, 50.8, 52.4, 52.8, 113.2, 116.0, 121.5, 125.4, 126.3, 126.4, 127.2, 127.4, 128.3, 129.0, 129.9, 130.0, 135.5, 135.8, 136.9, 140.2, 142.7, 164.0, 197.2. Anal. Calcd. for C31 H35 NO2 : C, 82.08; H, 7.78; N, 3.09 %. Found: C, 81.58; H, 7.38; N, 2.64 %. (E)-2-Ethyl-4-(4-methoxybenzylidene)-10-(4methoxyphenyl)-7,7-dimethyl-3,4,6,7,8,10-hexahydro-1Hchromeno[3,2-c]pyridin-9(2H)-one (9ak) White solid; Yield: 94 %, Mp.:90–91 ◦ C; 1 H NMR (300 MHz, CDCl3 ) δH 0.96 (d, J = 7.1 Hz, 3H), 0.99 (s, 2H), 1.03 (s, 3H), 1.11 (s, 6H), 2.21 (d, J = 5.3 Hz, 2H), 2.43 (dd, J = 8.3, 4.2 Hz, 3H), 2.52 (d, J = 4.7 Hz, 2H), 3.13 (d, J = 16.2 Hz, 1H), 3.33 (d, J = 13.9 Hz, 1H), 3.73 (d, J = 5.7 Hz, 2H), 3.77 (s, 3H), 3.83 (s, 3H), 4.20 (s, 1H), 6.79 (s, 1H), 6.82 (s, 1H), 6.92 (s, 2H), 7.20 (t, J = 8.5 Hz, 5H); 13 C NMR (75 MHz, CDCl3 ) δC 12.1, 27.6, 29.0, 32.1, 37.5, 41.2, 50.4, 50.8, 52.1, 52.8, 55.1, 55.2, 112.7, 113.4, 113.7, 114.2, 122.3, 125.5, 129.0, 129.1, 129.2, 130.4, 135.8, 140.5, 158.2, 158.6, 162.0, 163.7, 197.2. Anal. Calcd. for C31 H35 NO4 : C, 76.67; H, 7.26; N, 2.88 %. Found: C, 76.18; H, 6.88; N, 2.39 %. (E)-2-Ethyl-7,7-dimethyl-10-(naphthalen-1-yl)-4(naphthalen-1-ylmethylene)-3,4,6,7,8,10-hexahydro-1Hchromeno[3,2-c]pyridin-9(2H)-one (9al) White solid; Yield: 94 %, Mp.:91–92 ◦ C; 1 H NMR (300 MHz, CDCl3 ) δH 0.76 (d, J = 7.2 Hz, 3H), 0.96 (s, 1H), 1.08 (s, 3H), 1.16 (s, 3H), 2.02 (s, 1H), 2.19 (s, 1H), 2.23 (s, 1H), 2.65 (d, J = 5.2 Hz, 2H), 3.09–3.25 (m, 3H), 3.54 (d, J = 13.4 Hz, 1H), 3.73 (s, 1H),7.47 (dd, J = 6.8, 3.0 Hz, 4H), 7.54 (dd, J = 6.8, 3.1 Hz, 3H), 7.72 (d, J = 8.6 Hz, 1H), 7.78–7.90 (m, 5H), 8.06 (d, J = 6.2 Hz, 1H), 8.53 (s, 1H); 13 C NMR (75 MHz, CDCl3 ) δC 11.8, 27.6, 29.0, 32.1, 41.3, 50.1, 50.6, 52.2, 52.9, 54.1, 120.8, 123.3, 124.7, 124.9, 125.0, 125.1, 125.5, 125.9, 126.03, 126.1, 126.3, 126.5, 126.6, 126.9, 127.4, 127.8, 128.4, 128.5, 128.7, 129.4, 131.9, 133.4, 133.5, 135.6, 140.2, 164.1, 197.1. Anal. Calcd. for C37 H35 NO2 : C, 84.54; H, 6.71; N, 2.66 %. Found: C, 84.04; H, 6.26; N, 2.22 %. (E)-4-(4-Chlorobenzylidene)-10-(4-chlorophenyl)-2propyl-3,4,6,7,8,10-hexahydro-1H-chromeno[3,2c]pyridin-9(2H)-one (9am) White solid; Yield: 96 %, Mp.:81–82 ◦ C; 1 H NMR (300 MHz, CDCl3 ) δH 0.79 (t, J = 7.4 Hz, 3H), 1.36 (dd, J = 15.3, 7.6 Hz, 2H), 2.02 (dd, J = 11.1, 5.8 Hz, 2H), 2.27–2.38 (m, 4H), 2.58–2.69 (m, 2H), 2.82 (d, J = 16.1 Hz, 1H), 3.07

(d, J = 16.1 Hz, 1H), 3.33 (d, J = 13.9 Hz, 1H), 3.63 (d, J = 13.8 Hz, 1H), 4.26 (s, 1H), 6.91 (s, 1H), 7.17 (d, J = 8.4 Hz, 2H), 7.24 (s, 4H), 7.33 (d, J = 8.5 Hz, 2H); 13 C NMR (75 MHz, CDCl3 ) δC 11.6, 20.2, 20.3, 27.5, 36.9, 37.8, 52.8, 53.3, 58.9, 113.5, 115.2, 121.4, 127.9, 128.4, 128.5, 129.6, 130.3, 132.4, 132.8, 134.9, 140.7, 142.1, 165.7, 197.1. Anal. Calcd. for C28 H27 Cl2 NO2 : C, 70.00; H, 5.66; N, 2.92 %. Found: C, 69.62; H, 5.12; N, 2.56 %. (E)-4-(2-Methylbenzylidene)-2-propyl-10-(o-tolyl)3,4,6,7,8,10-hexahydro-1H-chromeno[3,2-c]pyridin-9(2H)one (9an) White solid; Yield: 98 %, Mp.:78–79 ◦ C; 1 H NMR (300 MHz, CDCl3 ) δH 0.75 (t, J = 7.4 Hz, 3H), 1.24–1.34 (m, 2H), 2.00–2.07 (m, 2H), 2.24 (dd, J = 9.0, 6.4 Hz, 2H), 2.32 (s, 3H), 2.37 (s, 2H), 2.59 (s, 3H), 2.63–2.73 (m, 2H), 2.77 (d, J = 5.3 Hz, 1H), 3.11 (d, J = 16.0 Hz, 1H), 3.19 (d, J = 13.6 Hz, 1H), 3.50 (d, J = 13.7 Hz, 1H), 4.51 (s, 1H), 6.97 (s, 1H), 7.05–7.10 (m, 3H), 7.13 (d, J = 2.4 Hz, 1H), 7.16 (s, 2H), 7.17–7.20 (m, 2H); 13 C NMR (75 MHz, CDCl3 ) δC 11.6, 19.8, 20.0, 20.1, 20.4, 27.6, 34.0, 36.9, 52.8, 53.2, 58.7, 114.5, 116.0, 121.3, 125.3, 126.3, 126.4, 127.2, 127.4, 128.4, 128.9, 129.9, 135.5, 135.9, 136.8, 140.0, 142.7, 165.7, 197.2. Anal. Calcd. for C30 H33 NO2 : C, 81.97; H, 7.57; N, 3.19 %. Found: C, 81.58; H, 7.07; N, 2.82 %. (E)-4-(4-Methoxybenzylidene)-10-(4-methoxyphenyl)-2propyl-3,4,6,7,8,10-hexahydro-1H-chromeno[3,2c]pyridin-9(2H)-one (9ao) White solid; Yield: 98 %, Mp.:76–77 ◦ C; 1 H NMR (300 MHz, CDCl3 ) δH 0.78 (t, J = 7.3 Hz, 3H), 1.36 (dt, J = 8.0, 5.0 Hz, 2H), 2.33 (dd, J = 13.0, 7.0 Hz, 4H), 2.57–2.75 (m, 2H), 2.87 (d, J = 16.0 Hz, 1H), 3.10 (d, J = 16.0 Hz, 1H), 3.38 (d, J = 13.8 Hz, 1H), 3.71 (d, J = 14.0 Hz, 2H), 3.77 (s, 3H), 3.83 (s, 3H), 3.86 (s, 1H), 4.22 (s, 1H), 6.80 (s, 1H), 6.82 (s, 1H), 6.89 (s, 1H), 6.91 (s, 2H), 7.17 (s, 1H), 7.21 (s, 1H), 7.24 (s, 1H), 7.26 (s, 1H); 13 C NMR (75 MHz, CDCl3 ) δC 11.6, 20.1, 20.3, 27.6, 36.9, 37.4, 52.7, 53.0, 55.1, 55.2, 58.4, 113.7, 114.0, 114.2, 122.2, 125.5, 129.0, 129.1, 130.4, 135.9, 140.5, 158.3, 158.6, 165.4, 197.3. Anal. Calcd. for C30 H33 NO4 : C, 76.41; H, 7.05; N, 2.97 %. Found: C, 76.01; H, 6.68; N, 2.52 %. (E)-10-(Naphthalen-1-yl)-4-(naphthalen-1-ylmethylene)-2propyl-3,4,6,7,8,10-hexahydro-1H-chromeno[3,2c]pyridin-9(2H)-one (9ap) White solid; Yield: 97 %, Mp.:95–96 ◦ C; 1 H NMR (300 MHz, CDCl3 ) δH 0.63 (t, J = 7.3 Hz, 3H), 1.14 (dd, J = 7.6, 3.6 Hz, 2H), 2.12 (dd, J = 16.1, 8.2 Hz, 4H), 2.32–2.38

123

Mol Divers

(m, 2H), 2.65 (d, J = 16.2 Hz, 1H), 2.78 (dt, J = 14.1, 5.4 Hz, 2H), 3.18 (dd, J = 14.9, 7.3 Hz, 2H), 3.53 (d, J = 13.7 Hz, 1H), 5.18 (s, 1H), 7.46 (dd, J = 7.1, 3.8 Hz, 4H), 7.51–7.55 (m, 2H), 7.56–7.63 (m, 2H), 7.72 (d, J = 9.0 Hz, 1H), 7.77–7.85 (m, 2H), 7.87 (d, J = 8.8 Hz, 2H), 8.52 (s, 1H), 8.04–8.09 (m, 1H); 13 C NMR (75 MHz, CDCl3 ) δC 11.4, 19.9, 20.4, 27.6, 36.8, 52.9, 53.5, 58.5, 114.5, 120.4, 123.4, 125.0, 125.1, 125.5, 125.6, 126.0, 126.1, 126.5, 127.3, 127.7, 128.3, 128.6, 128.8, 131.7, 131.9, 133.5, 140.2, 165.8, 197.2. Anal. Calcd. for C36 H33 NO2 : C, 84.51; H, 6.50; N, 2.74 %. Found: C, 84.01; H, 6.00; N, 2.26 %. (E)-4-(4-Chlorobenzylidene)-10-(4-chlorophenyl)-7,7dimethyl-2-propyl-3,4,6,7,8,10-hexahydro-1Hchromeno[3,2-c]pyridin-9(2H)-one (9aq) White solid; Yield: 95 % Mp.:80–81 ◦ C; 1 H NMR (300 MHz, CDCl3 ) δH 0.79 (t, J = 7.3 Hz, 3H), 1.02 (s, 3H), 1.11 (s, 3H), 1.36 (dd, J = 15.4, 7.6 Hz, 2H), 2.21 (d, J = 6.9 Hz, 2H), 2.27–2.32 (m, 2H), 2.53 (d, J = 2.8 Hz, 2H), 2.79 (d, J = 16.1 Hz, 1H), 3.09 (d, J = 16.2 Hz, 1H), 3.30 (d, J = 13.5 Hz, 1H), 3.66 (d, J = 13.8 Hz, 1H), 4.23 (s, 1H), 6.90 (s, 1H), 7.16 (d, J = 8.3 Hz, 3H), 7.27 (s, 2H), 7.33 (d, J = 8.2 Hz, 3H); 13 C NMR (75 MHz, CDCl3 ) δC 11.6, 20.2, 27.5, 28.9, 32.1, 37.9, 41.2, 50.7, 52.7, 53.3, 58.9, 112.2, 115.2, 121.4, 128.0, 128.5, 128.5, 128.8, 129.5, 130.3, 131.5, 132.4, 132.8, 133.6, 134.9, 140.6, 142.0, 147.4, 163.9, 197.0. Anal. Calcd. for C30 H31 Cl2 NO2 : C, 70.86; H, 6.15; N, 2.75 %. Found: C, 70.46; H, 5.74; N, 2.38 %. (E)-7,7-Dimethyl-4-(2-methylbenzylidene)-2-propyl-10-(otolyl)-3,4,6,7,8,10-hexahydro-1H-chromeno[3,2-c]pyridin9(2H)-one (9ar) White solid; Yield: 98 %, Mp.:74–75 ◦ C; 1 H NMR (300 MHz, CDCl3 ) υmax (KBr) = 1664, 1629, 1373, 1215 cm−1 ; δH 0.75 (t, J = 7.3 Hz, 3H), 1.06 (s, 3H), 1.12 (s, 3H), 1.25– 1.32 (m, 2H), 2.20 (d, J = 7.4 Hz, 2H), 2.24 (d, J = 2.9 Hz, 2H), 2.33 (s, 3H), 2.54 (d, J = 6.8 Hz, 2H), 2.59 (s, 3H), 2.74 (d, J = 16.1 Hz, 1H), 3.15 (dd, J = 14.8, 10.4 Hz, 2H), 3.52 (d, J = 13.8 Hz, 1H), 4.51 (s, 1H), 6.96 (s, 1H), 7.05–7.09 (m, 3H), 7.14 (d, J = 4.2 Hz, 3H), 7.19 (d, J = 3.5 Hz, 2H); 13 C NMR (75 MHz, CDCl3 ) δC 11.6, 19.8, 20.0, 20.1, 27.6, 29.0, 32.1, 32.2, 41.2, 50.7, 52.8, 53.2, 58.7, 113.2, 116.0, 121.4, 125.3, 125.5, 126.3, 126.4, 127.2, 127.4, 128.3, 128.8, 128.9, 129.8, 129.9, 130.3, 135.5, 135.8, 136.8, 140.1, 140.3, 142.6, 164.0, 197.1. Anal. Calcd. for C32 H37 NO2 : C, 82.19; H, 7.97; N, 3.00 %. Found: C, 81.74; H, 7.57; N, 2.66 %; ESI-MS m/z calc [M + H]+ 468.28, found 468.28.

123

(E)-4-(4-Methoxybenzylidene)-10-(4-methoxyphenyl)-7,7dimethyl-2-propyl-3,4,6,7,8,10-hexahydro-1Hchromeno[3,2-c]pyridin-9(2H)-one (9as) White solid; Yield: 96 %, Mp.:78–79 ◦ C; 1 H NMR (300 MHz, CDCl3 ) δH 0.79 (t, J = 7.4 Hz, 3H), 1.03 (s, 3H), 1.11 (s, 3H), 1.36 (d, J = 9.7 Hz, 2H), 2.21 (d, J = 5.0 Hz, 2H), 2.28–2.32 (m, 2H), 2.45 (s, 1H), 2.52 (d, J = 4.6 Hz, 2H), 2.83 (d, J = 15.9 Hz, 1H), 3.10 (d, J = 16.3 Hz, 1H), 3.32 (d, J = 13.3 Hz, 1H), 3.77 (s, 3H), 3.83 (s, 3H), 4.19 (s, 1H), 6.82 (s, 1H), 6.88–6.92 (m, 3H), 7.19 (t, J = 8.3 Hz, 4H), 7.38 (d, J = 8.7 Hz, 1H); 13 C NMR (75 MHz, CDCl3 ) δC 11.6, 20.2, 27.5, 28.9, 32.1, 37.5, 50.8, 52.9, 53.3, 55.1, 55.1, 55.2, 58.8, 112.6, 113.4, 113.7, 114.0, 114.5, 121.9, 125.9, 128.0, 129.0, 129.1, 129.2, 130.4, 132.2, 135.9, 136.0, 158.2, 158.5, 163.7, 197.1. Anal. Calcd. for C32 H37 NO4 : C, 76.92; H, 7.46; N, 2.80 %. Found: C, 76.54; H, 7.06; N, 2.40 %.

(E)-7,7-Dimethyl-10-(naphthalen-1-yl)-4-(naphthalen-1ylmethylene)-2-propyl-3,4,6,7,8,10-hexahydro-1Hchromeno[3,2-c]pyridin-9(2H)-one (9at) White solid; Yield: 95 %, Mp.:92–93 ◦ C; 1 H NMR (300 MHz, CDCl3 ) δH 0.77 (t, J = 7.1 Hz, 3H), 0.96 (s, 1H), 1.09 (d, J = 6.8 Hz, 3H), 1.16 (s, 3H), 2.02 (s, 1H), 2.24 (dd, J = 16.7, 11.3 Hz, 4H), 2.55 (d, J = 23.4 Hz, 1H), 2.65 (d, J = 5.2 Hz, 2H), 3.10–3.25 (m, 2H), 3.54 (d, J = 13.4 Hz, 1H), 3.73 (s, 1H), 7.28 (s, 1H), 7.46 (dd, J = 12.9, 5.3 Hz, 5H), 7.51–7.57 (m, 3H), 7.72 (d, J = 8.6 Hz, 1H), 7.77– 7.90 (m, 4H), 8.06 (d, J = 6.2 Hz, 1H); 13 C NMR (75 MHz, CDCl3 ) δC 11.4, 19.7, 27.6, 29.0, 32.1, 41.4, 50.7, 52.5, 53.0, 54.4, 58.0, 113.2, 121.0, 123.4, 124.8, 125.0, 125.1, 125.5, 125.9, 126.0, 126.1, 126.3, 126.5, 126.9, 127.4, 127.8, 128.4, 128.7, 129.3, 131.8, 131.9, 133.5, 133.6, 135.6, 140.1, 140.2, 164.1, 197.1. Anal. Calcd. for C38 H37 NO2 : C, 84.57; H, 6.91; N, 2.60 %. Found: C, 84.11; H, 6.55; N, 2.24 %.

(E)-2-Benzyl-4-(4-chlorobenzylidene)-10-(4chlorophenyl)-3,4,6,7,8,10-hexahydro-1H-chromeno[3,2c]pyridin-9(2H)-one (9au) White solid; Yield: 94 %, Mp.:83–84 ◦ C; 1 H NMR (300 MHz, CDCl3 ) δH 2.02 (dd, J = 11.0, 5.4 Hz, 2H), 2.31–2.38 (m, 2H), 2.60–2.71 (m, 2H), 2.83 (d, J = 16.1 Hz, 1H), 3.06 (d, J = 16.2 Hz, 1H), 3.45 (dd, J = 24.6, 12.8 Hz, 3H), 3.72 (d, J = 13.8 Hz, 1H), 4.18 (s, 1H), 6.92 (s, 1H), 7.10 (d, J = 8.2 Hz, 4H), 7.20 (t, J = 6.0 Hz, 8H), 7.29 (s, 1H); 13 C NMR (75 MHz, CDCl3 ) δC 20.3, 27.5, 36.8, 37.6, 52.4, 52.8, 60.7, 113.5, 115.0, 121.6, 127.2, 127.7, 128.2, 128.4, 128.5, 128.9, 129.5, 130.3, 132.4, 132.8, 134.8, 137.2, 140.7, 142.1,

Mol Divers

165.7, 197.1. Anal. Calcd. for C32 H27 Cl2 NO2 : C, 72.73; H, 5.15; N, 2.65 %. Found: C, 72.36; H, 4.78; N, 2.26 %. (E)-2-Benzyl-4-(2-methylbenzylidene)-10-(o-tolyl)3,4,6,7,8,10-hexahydro-1H-chromeno[3,2-c]pyridin-9(2H)one (9av) White solid; Yield: 98 %, Mp.:72–73 ◦ C; 1 H NMR (300 MHz, CDCl3 ) δH 1.98–2.09 (m, 2H), 2.31 (s, 3H), 2.35 (d, J = 5.3 Hz, 2H), 2.47 (s, 3H), 2.60–2.68 (m, 1H), 2.69– 2.81 (m, 2H), 3.10 (d, J = 16.2 Hz, 1H), 3.27 (d, J = 14.0 Hz, 1H), 3.40 (dd, J = 34.1, 12.6 Hz, 2H), 3.56–3.65 (m, 1H), 4.43 (s, 1H), 7.01 (dd, J = 7.8, 4.4 Hz, 4H), 7.08 (d, J = 2.3 Hz, 3H), 7.15 (s, 1H), 7.15–7.19 (m, 6H); 13 C NMR (75 MHz, CDCl3 ) δC 19.7, 20.0, 20.4, 27.6, 33.7, 36.9, 52.5, 52.6, 60.4, 114.6, 115.8, 121.6, 125.3, 126.3, 126.4, 127.1, 127.2, 128.1, 128.3, 128.9, 129.1, 129.9, 130.0, 135.4, 136.0, 136.7, 137.4, 140.1, 142.8, 165.8, 197.2. Anal. Calcd. for C34 H33 NO2 : C, 83.74; H, 6.82; N, 2.87 %. Found: C, 83.36; H, 6.42; N, 2.47 %. (E)-2-Benzyl-4-(4-methoxybenzylidene)-10-(4methoxyphenyl)-3,4,6,7,8,10-hexahydro-1H-chromeno[3,2c]pyridin-9(2H)-one (9aw) White solid; Yield: 97 %, Mp.:70–71 ◦ C; 1 H NMR (300 MHz, CDCl3 ) δH 1.96–2.06 (m, 2H), 2.30–2.38 (m, 2H), 2.60–2.70 (m, 2H), 2.87 (d, J = 16.0 Hz, 1H), 3.07 (d, J = 16.1 Hz, 1H), 3.43 (d, J = 12.6 Hz, 2H), 3.55 (d, J = 12.9 Hz, 1H), 3.77 (s, 3H), 3.82 (s, 3H), 3.85 (d, J = 5.2 Hz, 1H), 4.14 (s, 1H), 6.80 (d, J = 8.6 Hz, 2H), 6.85 (d, J = 8.7 Hz, 2H), 6.93 (s, 1H), 7.11 (d, J = 6.2 Hz, 3H), 7.15 (s, 1H), 7.16–7.22 (m, 5H); 13 C NMR (75 MHz, CDCl3 ) δC 20.4, 27.6, 37.0, 37.3, 52.7, 52.9, 55.1, 55.2, 60.8, 113.7, 113.7, 114.0, 114.1, 114.5, 122.0, 125.8, 127.1, 128.1, 129.0, 129.1, 129.2, 130.4, 132.2, 136.0, 137.6, 140.6, 158.3, 158.5, 165.5, 197.3. Anal. Calcd. for C34 H33 NO4 : C, 78.59; H, 6.40; N, 2.70 %. Found: C, 78.09; H, 5.98; N, 2.28 %. (E)-2-Benzyl-10-(naphthalen-1-yl)-4-(naphthalen-1ylmethylene)-3,4,6,7,8,10-hexahydro-1H-chromeno[3,2c]pyridin-9(2H)-one (9ax) White solid; Yield: 98 %, Mp.:94–95 ◦ C; 1 H NMR (300 MHz, CDCl3 ) δ1H H NMR (300 MHz, CDCl3 ) δH 2.04–2.09 (m, 2H), 2.34–2.38 (m, 2H), 2.65–2.83 (m, 4H), 3.17–3.28 (m, 2H), 3.35 (d, J = 12.7 Hz, 1H), 3.52–3.66 (m, 1H), 5.11 (s, 1H), 6.87 (d, J = 7.0 Hz, 2H), 6.99–7.08 (m, 3H), 7.16 (d, J = 7.0 Hz, 1H), 7.37 (dd, J = 13.3, 6.0 Hz, 1H), 7.42–7.57 (m, 7H), 7.75 (dd, J = 8.7, 5.1 Hz, 2H), 7.85 (dd, J = 8.2, 5.0 Hz, 2H), 8.08 (d, J = 6.6 Hz, 1H), 8.41 (d, J = 8.3 Hz, 1H). 13 C NMR (75 MHz, CDCl3 ) δC 20.5,

27.8, 36.9, 52.5, 53.2, 54.1, 60.2, 114.6, 116.4, 120.7, 123.4, 124.9, 125.0, 125.1, 125.5, 125.6, 125.9, 126.0, 126.1, 126.6, 126.9, 127.4, 127.6, 127.9, 128.4, 128.6, 128.7, 129.0, 131.8, 132.0, 133.6, 133.7, 137.3, 140.3, 154.9, 165.9, 197.1 Anal. Calcd. for C40 H33 NO2 : C, 85.84; H, 5.94; N, 2.50 %. Found: C, 85.44; H, 5.54; N, 2.00 %. (E)-2-Benzyl-4-(4-chlorobenzylidene)-10-(4chlorophenyl)-7,7-dimethyl-3,4,6,7,8,10-hexahydro-1Hchromeno[3,2-c]pyridin-9(2H)-one (9ay) White solid; Yield: 95 %, Mp.:73–74 ◦ C; 1 H NMR (300 MHz, CDCl3 ) δH 1.03 (s, 3H), 1.11 (s, 3H), 2.21 (d, J = 6.9 Hz, 2H), 2.46–2.54 (m, 2H), 2.81 (d, J = 16.2 Hz, 1H), 3.08 (d, J = 16.2 Hz, 1H), 3.40–3.51 (m, 2H), 3.70–3.83 (m, 2H), 4.16 (s, 1H), 6.91 (s, 1H), 7.09 (d, J = 8.2 Hz, 3H), 7.20–7.25 (m, 8H), 7.29 (s, 1H), 7.33 (s, 1H); 13 C NMR (75 MHz, CDCl3 ) δC 27.5, 29.0, 32.1, 37.7, 41.2, 50.7, 52.3, 52.7, 60.6, 112.2, 114.9, 121.7, 127.3, 127.6, 128.2, 128.4, 128.5, 128.8, 129.0, 129.5, 130.2, 131.4, 132.4, 132.8, 133.5, 134.8, 135.3, 137.1, 140.6, 142.0, 164.0, 197.0. Anal. Calcd. for C34 H31 Cl2 NO2 : C, 73.38; H, 5.61; N, 2.52 %. Found: C, 72.87; H, 5.16; N, 2.02 %. (E)-2-Benzyl-7,7-dimethyl-4-(2-methylbenzylidene)-10-(otolyl)-3,4,6,7,8,10-hexahydro-1H-chromeno[3,2-c]pyridin9(2H)-one (9az) White solid; Yield: 98 %, Mp.:76–77 ◦ C; 1 H NMR (300 MHz, CDCl3 ) δH 1.06 (s, 3H), 1.12 (s, 3H), 2.19 (d, J = 7.2 Hz, 2H), 2.32 (s, 3H), 2.47 (s, 3H), 2.55 (d, J = 6.9 Hz, 2H), 3.12 (d, J = 16.3 Hz, 1H), 3.25 (d, J = 13.9 Hz, 1H), 3.34 (d, J = 12.6 Hz, 1H), 3.46 (d, J = 12.6 Hz, 1H), 3.58–3.73 (m, 2H), 4.43 (s, 1H), 6.97 (d, J = 6.6 Hz, 2H), 7.03 (s, 2H), 7.07 (d, J = 3.9 Hz, 2H), 7.17 (dd, J = 7.2, 5.1 Hz, 8H); 13 C NMR (75 MHz, CDCl3 ) δC 19.7, 19.9, 20.04, 27.6, 29.1, 32.1, 41.3, 50.7, 52.5, 52.6, 60.5, 113.2, 115.7, 121.7, 125.3, 125.4, 126.3, 126.4, 127.1, 127.2, 128.1, 128.2, 128.3, 128.7, 128.9, 129.0, 129.1, 129.9, 130.0, 130.2, 135.4, 135.9, 136.1, 136.7, 137.4, 138.0, 140.2, 164.0, 197.1. Anal. Calcd. for C36 H37 NO2 : C, 83.85; H, 7.23; N, 2.72 %. Found: C, 83.45; H, 6.86; N, 2.24 %. (E)-2-Benzyl-4-(4-methoxybenzylidene)-10-(4methoxyphenyl)-7,7-dimethyl-3,4,6,7,8,10-hexahydro-1Hchromeno[3,2-c]pyridin-9(2H)-one (9aaa) White solid; Yield: 96 %, Mp.:71–72 ◦ C; 1 H NMR (300 MHz, CDCl3 ) υmax (KBr) = 1664, 1627, 1373, 1251 cm−1 ; δH 1.03 (s, 3H), 1.11 (s, 3H), 2.20 (d, J = 5.8 Hz, 2H), 2.52 (d, J = 4.6 Hz, 2H), 2.85 (d, J = 16.2 Hz, 1H), 3.09 (d, J = 16.2 Hz, 1H), 3.45 (s, 1H), 3.54 (d, J = 12.9 Hz, 1H),

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Mol Divers

3.77 (s, 3H), 3.81 (s, 3H), 3.84 (s, 2H), 4.11 (s, 1H), 6.78– 6.84 (m, 3H), 6.86 (s, 1H), 6.90 (d, J = 8.2 Hz, 2H), 7.11 (s, 2H), 7.15 (d, J = 4.7 Hz, 2H), 7.20 (d, J = 6.6 Hz, 4H); 13 C NMR (75 MHz, CDCl ) 3 δC 27.5, 29.0, 32.1, 37.4, 41.3, 50.8, 52.7, 54.4, 55.1, 55.2, 60.8, 112.7, 113.4, 113.7, 114.0, 114.5, 122.1, 125.8, 127.1, 128.1, 128.3, 128.9, 129.0, 130.3, 131.4, 132.2, 136.0, 137.5, 140.5, 158.2, 158.5, 163.7, 197.1. Anal. Calcd. for C36 H37 NO4 : C, 78.95; H, 6.81; N, 2.56 %. Found: C, 78.45; H, 6.41; N, 2.06 %; ESI-MS m/z calc [M + H]+ 548.27, found 548.29. (E)-2-Benzyl-7,7-dimethyl-10-(naphthalen-1-yl)-4(naphthalen-1-ylmethylene)-3,4,6,7,8,10-hexahydro-1Hchromeno[3,2-c]pyridin-9(2H)-one (9aab) White solid; Yield: 98 %, Mp.:106–107 ◦ C; 1 H NMR (300 MHz, CDCl3 ) δH 0.96 (s, 1H), 1.10 (dd, J = 17.6, 15.1 Hz, 6H), 2.11–2.30 (m, 2H), 2.61 (dd, J = 28.0, 21.0 Hz, 3H), 3.26 (dt, J = 17.8, 12.4 Hz, 3H), 3.53–3.65 (m, 1H), 3.77 (s, 1H), 6.87 (d, J = 6.9 Hz, 1H), 7.03 (dt, J = 13.9, 6.9 Hz, 4H), 7.15 (d, J = 7.1 Hz, 1H), 7.36 (dd, J = 13.8, 6.4 Hz, 2H), 7.43 (d, J = 7.8 Hz, 1H), 7.46–7.52 (m, 4H), 7.53 (d, J = 3.2 Hz, 1H), 7.74 (t, J = 7.1 Hz, 2H), 7.86 (t, J = 10.2 Hz, 3H), 8.06–8.10 (m, 1H); 13 C NMR (75 MHz, CDCl3 ) δC 27.7, 29.1, 32.1, 41.4, 50.7, 52.5, 53.1, 54.0, 60.3, 120.7, 123.3, 124.7, 124.9, 125.1, 125.5, 125.9, 126.0, 126.2, 126.6, 126.9, 127.0, 127.6, 127.9, 128.0, 128.4, 128.5, 128.6, 128.9, 129.0, 129.3, 131.9, 132.2, 133.4, 134.8, 135.6, 137.1, 140.2, 164.2, 174.8, 197.1. Anal. Calcd. for C42 H37 NO2 : C, 85.83; H, 6.35; N, 2.38 %. Found: C, 85.43; H, 5.96; N, 1.98 %. Acknowledgments RRK thanks the University Grants Commission, New Delhi for funds through Major Research Project F. No. 42242/2013 (SR) and Department of Science and Technology, New Delhi for funds under (i) IRHPA program for the high resolution NMR facility in the Department and (ii) PURSE program. RVS thanks the University Grants Commission, New Delhi for research fellowship.

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