Helvetica Chimica Acta ± Vol. 85 (2002)
2461
1H-NMR (CDCl
, 300 MHz): 6.96 (d, J 4, 1 H); 6.33 (s, 1 H); 6.15 (d, J 7.8, 1 H); 5.94 ± 5.88 (m, 3 H); 4.94
3
(
(
d, J 5.8, 1 H); 4.08 (s, 3 H); 3.98 (s, 3 H); 3.84 (s, 3 H); 2.80 ± 2.75 (m, 1 H); 2.62 ± 2.53 (m, 2 H); 2.31 ± 2.18
m, 1 H); 2.04 ± 1.96 (br. s, 1 H). MS: 400 ([M H] ). Anal. calc. for C21
7
H21NO : C 63.15, H 5.30, N 3.51; found:
C 63.35, H 5.45, N 3.42.
General Procedure 2 (5a ± 13a, and 5b): N-(3-Chlorophenyl)-1-(1,3-dihydro-4,5-dimethoxy-3-oxoisobenzo-
furan-1-yl)-1,2,3,4-tetrahydro-8-methoxy-6,7-(methylenedioxy)isoquinoline-2-carboxamide (5a). A soln. of 3-
chlorophenyl isocyanate (0.385 g, 2.5 mmol) in dry MeCN (5 ml) was added dropwise to a soln. of 3a (1 g,
2
.5 mmol) in dry MeCN (15 ml) at 58. The soln. was stirred at 258 for 2 h. The mixture was then poured into H
and extracted with CHCl . The extract was dried (Na SO ), and the solvent was evaporated under reduced
pressure to give 1.3 g of 5a, which was purified by CC (silica gel 60 H; AcOEt/hexane, 1:5). Yield 1.3 g (87%).
2
O
3
2
4
2
0
M.p. 202 ± 2038. [a]
D
197 (c 20 mg, CHCl
3
). IR: 3395 (br.), 3386 (br.), 2939m, 1751s, 1660s, 1587s, 1481s,
, 300 MHz): 7.49 (s, 1 H); 7.26 ± 7.17 (m, 2 H); 6.52 (d, J 8.8, 1 H);
1
1
259s, 1028m, 921m, 775m. H-NMR (CDCl
3
7
.05 (AB, J 8.8, 2 H); 6.99 (AB, J 8.8, 2 H); 6.38 (s, 1 H); 6.09 (d, J 2.9, 1 H); 5.71 (d, J 2.9, 1 H); 5.93
(
s, 2 H); 7.34 (br. s, 1 H); 4.05 (s, 3 H); 3.98 (s, 3 H); 3.87 (s, 3 H); 3.82 ± 2.28 (m, 4 H). MS: 553 ([M H] ).
2 8
Anal. calc. for C28H25ClN O : C 60.82, H 4.55, N 5.06; found: C 60.48, H 4.46, N 5.10.
N-(4-Chlorophenyl)-1-(1,3-dihydro-4,5-dimethoxy-3-oxoisobenzofuran-1-yl)-1,2,3,4-tetrahydro-8-methoxy-
2
0
6
,7-(methylenedioxy)isoquinoline-2-carboxamide (6a). Yield 85%. M.p. 173 ± 1748. [a]
D
233 (c 20 mg,
1
CHCl
3
). IR: 3395 (br.), 2941m, 1753s, 1658s, 1593m, 1494s, 1263s, 1012m, 829m. H-NMR (CDCl
3
, 300 MHz):
7
.34 (br. s, 1 H); 7.23 (d, J 8.4, 2 H); 7.14 (d, J 8.4, 2 H); 6.95 (d, J 8.4, 1 H); 6.41 (d, J 8.4, 1 H); 6.28
(
2
s, 1 H); 6.10 (d, J 2.8, 1 H); 5.84 (s, 2 H); 5.61 (d, J 2.8, 1 H); 3.96 (s, 3 H); 3.89 (s, 3 H); 3.77 (s, 3 H); 3.79 ±
.10 (m, 4 H). MS: 553 ([M H] ). Anal. calc. for C28
2 8
H25ClN O : C 60.82, H 4.55, N 5.06; found: C 60.75,
H 4.61, N 5.05.
N-(2,4-Dichlorophenyl)-1-(1,3-dihydro-4,5-dimethoxy-3-oxoisobenzofuran-1-yl)-1,2,3,4-tetrahydro-8-meth-
2
0
oxy-6,7-(methylenedioxy)isoquinoline-2-carboxamide (7a). Yield 73%. M.p. 93 ± 948. [a]
CHCl
D
128 (c 20 mg,
1
3
) IR: 3379s, 2941m, 1765s, 1676s, 1579m, 1498s, 1263s, 1028s, 750w. H-NMR (CDCl
3
, 300 MHz): 8.04
(
8
3
d, J 8.4, 1 H); 7.52 (br. s, 1 H); 7.38 (d, J 4.2, 1 H); 7.19 (d, J 4.2, 1 H); 7.09 (d, J 8.4, 1 H); 6.72 (d, J
.4, 1 H); 6.38 (s, 1 H); 6.05 (d, J 4.2, 1 H); 5.91 (s, 2 H); 5.86 (d, J 4.2, 1 H); 4.04 (s, 3 H); 3.88 (s, 2 Â 3 H);
.72 ± 2.72 (m, 4 H). MS: 588 ([M H] ). Anal. calc. for C28
2 2 8
H24Cl N O : C 57.25, H 4.11, N 4.76; found:
C 56.92, H 4.12, N 4.73.
N-(2,4-Difluorophenyl)-1-(1,3-dihydro-4,5-dimethoxy-3-oxobenzofuran-1-yl)-1,2,3,4-tetrahydro-8-methoxy-
6
2
0
,7-(methylenedioxy)-isoquinoline-2-carboxamide (8a). Yield 83%. M.p. 170 ± 1718. [a]
D
163 (c 20 mg,
1
CHCl
3
) IR: 3357 (br.), 2941m, 1759s, 1662s, 1612m, 1498s, 1259s, 1020m, 846w, 752w. H-NMR (CDCl
3
,
3
1
00 MHz): 7.85 (q, J 9.1, 1 H); 7.17 (br. s, 1 H); 7.07 (d, J 9.1, 1 H); 6.87 (q, J 9.1, 2 H); 6.63 (d, J 9.1,
H); 6.38 (s, 1 H); 6.07 (d, J 4.5, 1 H); 5.92 (s, 2 H); 5.81 (d, J 4.5, 1 H); 4.05 (s, 3 H); 3.91 (s, 3 H); 3.87
(
s, 3 H); 3.77 ± 2.52 (m, 4 H). MS: 555 ([M H] ). Anal. calc. for C28
24 2 2 8
H F N O : C 60.65, H 4.36, N 5.05;
found: C 60.83, H 4.31, N 5.12.
1
-(1,3-Dihydro-4,5-dimethoxy-3-oxoisobenzofuran-1-yl)-1,2,3,4-tetrahydro-8-methoxy-6,7-(methylene-
2
0
dioxy)-N-phenylisoquinoline-2-carbothioamide (9a). Yield 86%. M.p. 181 ± 1828. [a]
CHCl
D
203 (c 20 mg,
1
3
) IR: 3336 (br.), 2952m, 1747s, 1596m, 1498s, 1261s, 1045m, 763w. H-NMR (CDCl
3
, 300 MHz): 7.94
(
1
br. s, 1 H); 7.42 ± 7.34 (m, 4 H); 7.13 (d, J 9, 1 H); 6.97 (s, 1 H); 6.49 (s, 1 H); 6.40 (s, 1 H); 6.28 (d, J 4.5,
H); 5.90 (s, 2 H); 4.24 (s, 1 H); 4.05 (s, 3 H); 3.89 (s, 3 H); 3.80 (s, 3 H); 2.96 ± 2.91 (m, 4 H). MS: 535 ([M
H] ). Anal. calc. for C28
26 2 7
H N O S: C 62.91, H 4.90, N 5.24; found: C 62.74, H 4.88, N 5.20.
N-(Chlorophenyl)-1-(1,3-dihydro-4,5-dimethoxy-3-oxobenzofuran-1-yl)-1,2,3,4-tetrahydro-8-methoxy-6,7-
2
0
(
methylenedioxy)isoquinoline-2-carbothioamide (10a). Yield 85%. M.p. 181 ± 1828. [a]
D
158 (c 20 mg,
1
CHCl
3
) IR: 3327 (br.), 2925m, 1745s, 1589m, 1500s, 1263s, 1045m, 804m. H-NMR (CDCl
3
, 300 MHz): 8.08
(
(
5
d, J 9.2, 1 H); 8.01 (br. s, 1 H); 7.47 ± 7.16 (m, 2 H); 7.13 (d, J 9.2, 1 H); 6.86 (s, 1 H); 6.40 (s, 2 H); 6.27
d, J 4.6, 1 H); 5.92 (s, 2 H); 4.30 (s, 1 H); 4.06 (s, 3 H); 3.89 (s, 3 H); 3.87 (s, 3 H); 2.89 ± 2.17 (m, 4 H). MS:
69 ([M H] ). Anal. calc. for C28
2 7
H25ClN O S: C 59.10, H 4.42, N 4.92; found: C 59.05, H 4.40, N 4.88.
1
-(1,3-Dihydro-4,5-dimethoxy-3-oxoisobenzofuran-1-yl)-1,2,3,4-tetrahydro-8-methoxy-N-(2-methoxyphen-
2
0
yl)-6,7-(methylenedioxy)isoquinoline-2-carbothioamide (11a). Yield 78%. M.p. 108 ± 1098. [a]
2
D
207 (c
1
0 mg, CHCl
3
) IR: 3386 (br.), 2939m, 1762s, 1600m, 1498s, 1263s, 750m. H-NMR (CDCl
3
, 300 MHz): 8.11
(
8
3
d, J 8.5, 1 H); 8.05 (br. s, 1 H); 7.17 (d, J 8.5, 1 H); 7.11 (d, J 8.5, 1 H); 6.99 (d, J 8.5, 1 H); 6.93 (d, J
.5, 1 H); 6.72 (s, 1 H); 6.40 (s, 1 H); 6.28 (d, J 4.3, 1 H); 5.87 (s, 2 H); 4.03 (s, 3 H); 3.93 (s, 3 H); 3.89 (s, 3 H);
.68 (s, 3 H); 3.20 ± 2.17 (m, 4 H). MS: 565 ([M H] ). Anal. calc. for C29
29 2 8
H N O S: C 61.58, H 5.16, N 4.95;
found: C 61.46, H 5.14, N 4.92.