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S. Koul et al. / Bioorg. Med. Chem. 8 (2000) 251±268
(6H, s, -C (CH3)2), 1.62 (4H, m, 2ÂCH2), 1.80 (2H, t,
J=6.5 Hz, Ar CH2 CH2), 2.75 (2H, t, J=6.5 Hz, Ar-
CH2 CH2), 3.58 (2H, m, -N (CH2)2), 6.40 (1H, d,
J=14.0 Hz, -CHCH CO), 6.60±6.92 (3H, m, ole®nic
and Ar H) and 7.04±7.68 (3H, m, ole®nic and Ar H)
Preparation of 3-[(2H)-2,2-dimethyl-3,4-dihydrobenzo-
pyran-6yl]-2E-propenoic acid (7). Compound 7 was pre-
pared from 1g (6.0 g, 32 mmol) and malonic acid (4.2 g,
40 mmol) as described for 6 to give crystalline com-
pound 736 (6.7 g, 90%), mp 188 ꢀC analysed for
C14H16O3, MS (%) M+ at m/z 232 (93), 215 (13), 188
1
Preparation of 5-[(2H)-2,2-dimethyl-3,4-dihydrobenzo-
pyran-6yl]-2E,4E-pentadienoic acid n-pentyl amide (31).
Compound 4g (1.0 g, 4 mmol) was condensed with n-
pentyl amine (0.6 mL) as described for 8 to yield 31, a solid
(1.20 g, 92%), mp 137 ꢀC (analysed for C21H29NO2; found
C 77.0317, H 8.9267, N 4.2793; calcd C 77.0253, H 8.9258,
N 4.2774). MS (%) M+ at m/z 327 (22), 241 (23), 185 (22),
(6), 176 (100) and 131 (20). ucm (KBr) 2964, 1674,
1609, 1574, 1494, 1430, 1386, 1370, 1304, 1286, 1260,
1234, 1150, 932 and 820. 1H NMR (CDCl3) d 1.32 (6Hs,
-C(CH3)2), 1.82 (2H, t, J=7.0 Hz, Ar CH2 CH2), 2.74
(2H, t, J=7.0 Hz, Ar CH2 CH2), 6.72 (1H, d,
J=15.0 Hz, CHCH CO), 6.80 (1H, d, J=8.5 Hz,
Ar H), 7.24 (1H, s, Ar H), 7.28 (1H, d, J=8.5 Hz,
Ar H) and 7.68 (1H, d, J=15.0 Hz, -CHCH CO).
1
175 (13), 157 (77), 128 (49), 96 (28) and 69 (100). ucm
(KBr) 3270, 2910, 1640, 1600, 1490, 1380, 1260, 1125, 1000,
920 and 805. 1H NMR (CDCl3) d 0.90 (3H, t, J=6.0Hz,
-CH2 CH3), 1.16±1.56 [12H, bs, -NH CH2 (CH2)3 and
C (CH3)2], 1.80 (2H, t, J=6.0 Hz, Ar CH2 CH2), 2.72
(2H, t, J=6.0 Hz, Ar CH2 CH2), 3.34 (2H, m,
-N (CH2)), 5.94 (1H, d, J=15.0 Hz, -CHCH CO),
6.52±6.82 and 6.90±7.66 (6H, m, ole®nic and Ar H).
Preparation of 3-[(2H)-2,2-dimethyl-3,4-dihydro-benzo-
pyran-6yl]-2E-propenoic acid piperidine amide (34).
Compound 7 (0.93 g, 4 mmol) was condensed with
piperidine (0.6 mL) as described for 8 to give 34 (1.10 g,
92%), mp 122 ꢀC (analysed for C19H25NO2; found C
76.2221, H 8.4160, N 4.6802; calcd C 76.2191, H 8.4156,
N 4.6781) MS (%) M+at m/z 299 (100), 214 (93), 187
1
Preparation of 3-(3,4-methylenedioxy phenyl)-2E-prope-
noic acid (6). To 1h (4.5 g, 30 mmol) in pyridine
(25 mL) and piperidine (1 mL) was added malonic acid
(3.7 g, 36 mmol) and contents stirred for 24 h, followed
by heating on water bath for 6 h. The contents were
cooled, poured in ice-cold water, acidi®ed with 2 N
HCl. The resulting precipitate ®ltered, washed with
water and air dried to give 6 (6.2 g, 95%), crystallised
from ethyl acetate:n-hexane (9:1), mp. 244±646 ꢀC (lit.
mp 247 ꢀC).35
(31), 158 (60) 84 (61) and 69 (30). ucm (KBr) 2932,
1640, 1598, 1578, 1494, 1434, 1382, 1368, 1270, 1244,
1232, 1214, 1110, 1010, 982 and 830. 1H NMR (CDCl3)
d: 1.23 (6H, s, -C(CH3)2), 1.56 (6H, bs, N C (CH2)3),
1.72 (2H, t, J=6.5 Hz, Ar CH2 CH2), 2.72 (2H, t,
J=6.5 Hz, Ar CH2 CH2), 3.50 (4H, m, NH (CH2)2),
6.66 (1H, d, J=15.0 Hz, CHCH CO), 6.62 (1H, d,
J=8.5 Hz, Ar H), 7.06±7.24 (2H, m, 2ÂAr-H) and
7.43 (1H, d, J= 15.0 Hz, -CHCH CO).
Preparation of 3-[(2H)-2,2-dimethyl-3,4-dihydrobenzo-
pyran-6yl]-2E-propenoic acid isopropyl amide (35).
Compound 7 (1.2 g, 5 mmol) was condensed with iso-
propyl amine (0.7 mL) by the method as described for 8
to give 35 (1.24 g, 91%), mp 89 ꢀC (analysed for C17
H23NO2; found C 74.6898, H 8.4823, N 5.1255; calcd C
74.6900, H 8.4816, N 5.1236); MS (%) M+ at m/z 273
(100), 215 (61), 188 (58), 159 (51) and 58 (48). ucm 1(KBr)
3260, 2968, 1654, 1612, 1580, 1496, 1420, 1384, 1370,
Preparation of 3-(3,4-methylenedioxy phenyl)-2E-prope-
noic acid piperidine amide (32). Compound 6 (2.1 g,
11 mmol) was condensed with piperidine (1.2 mL) as
described for 8 to yield 32 (2.80 g, 91%), mp 89 ꢀC
(analysed for C15H17NO3; found C 69.4901, H 6.6089,
N 5.4071; calcd C 69.4804, H 6.6078, N 5.4017) MS (%)
M+ at m/z 259 (4), 147 (21), 111 (100) and 84 (29).
1
ucm (KBr) 2940, 1642, 1588, 1494, 1436, 1350, 1298,
1250, 1216, 1100, 1018, 972 and 808. 1H NMR (CDCl3)
1304, 1236, 1200, 1152, 1112, 1000, 920 and 874. H
1
d
1.64 (6H, bs, N C (CH2)3), 3.60 (4H, bs,
NMR (CDCl3) d 1.20 (6H, d, J=6.5 Hz, -C(CH3)2),
1.33 (6H, s, (CH3)2), 1.76 (2H, t, J=6.50 Hz, Ar CH2
CH2), 2.70 (2H, t, J=6.5 Hz, Ar CH2), 4.13 (1H, m,
CH N), 6.13 (1H, d, J=15.0 Hz, CHCH CO), 6.63
(1H, d, J=8.5 Hz, Ar H), 6.95±7.23 (2H, m, Ar H)
and 7.43 (1H, d, J=15.0 Hz, -CHCH CO).
-N (CH2)2), 5.94 (2H, s, -OCH2O-), 6.70 (1H, d,
J=15.0 Hz, CHCH CO), 6.76 (1H, d, J=8.5 Hz,
Ar H), 6.98 (1H, d, J=8.5 Hz, Ar H), 7.02 (1H, s,
Ar H) and 7.52 (1H, d, J=15.0 Hz, CH=CH CO).
Preparation of 3-(3,4-methylenedioxy phenyl)-2E-prope-
noic acid pyrrolidine amide (33). Compound 6 (2.0 g,
10 mmol) was condensed with pyrrolidine (1.0 mL) as
described for 8 to yield 33 (2.4 g, 90%), mp 146 ꢀC
(analysed for C14H15NO3; found C 68.5603, H 6.1644,
N 5.7133; calcd C 68.5569, H 6.1638, N 5.7106). MS
(%) M+ at m/z 245 (15) 174 (32) 147 (9) 98 (30) and
70 (100). ucm 1(KBr) 2960, 1646, 1594, 1496, 1454,
1414, 1354, 1320, 1278, 1242, 1198, 1018, 992, 928 and
Preparation of 3-[(2H)-2,2-dimethyl-3,4-dihydrobenzo-
pyran-6yl-2E- propenoic acid n-butylamide (36). Com-
pound 7 (1.2g, 5 mmol) was condensed with n-butylamine
(0.6 mL) by the method as described for 8 to give 36
(1.29 g, 90%), mp 86ꢀC (analysed for C18H25NO2; found
C 75.2301, H 8.7677, N 4.8771; calcd C 75.2253, H 8.7673,
N 4.8736). MS (%) M+ at m/z 287 (100), 242 (79), 214
(79), 187 (21), 170 (12), 158 (60) 130 (30) and 72 (14).
1
1
826. H NMR (CDCl3) d 1.92 (4H, bs, N C (CH2)2),
ucm (KBr) 3200, 2932, 1648, 1616, 1580, 1544, 1450,
3.56 (4H, m, -N (CH2)2), 5.96 (2H, s, -OCH2O-),
6.50 (1H, d, J=15.0 Hz, CHCH CO), 6.78 (1H, d,
J=8.5Hz, Ar-H), 6.97 (1H, d, J=8.5Hz, Ar-H), 7.00
(1H, s, Ar-H) and 7.56 (1H, d, J=15.0 Hz, CH
CH CO).
1424, 1384, 1370, 1308, 1264, 1236, 1152, 968 and 852. 1H
NMR (CDCl3) d 0.92 (3H, t, J= 6.5 Hz, -CH2 CH3),
1.33 (6H, s, -C(CH3)2), 1.49 (4H, m, -C (CH2)2), 1.79
(2H, t, J=6.5 Hz, Ar CH2 CH2), 2.74 (2H, t, J=6.5 Hz,
Ar CH2 CH2), 3.34 (2H, m, NH-CH2), 6.38 (1H, d,