5
=CH), 3.77 (3H, s, OMe), 3.71 (3H, s, OMe), 3.67 (3H, s, OMe),
4.2.6.
6-Amino-8-(4-methoxyphenyl)-8,8a-dihydro-1H-
ACCEPTED MANUSCRIPT
3.49 (1H, d, J 12.5 Hz, CHAr), 3.31 (1H, dd, J 18.0, 2.0 Hz,
=CHCHaHbN), 3.00−2.97 (1H, m, CHCH2N), 2.60 (1H, ddd, J
18.0, 2.0, 2.0 Hz, =CHCHaHbN), 2.49 (1H, dd, J 11.0, 5.0 Hz,
CHCHaHbN), 2.11 (3H, s, NMe), 1.65 (1H, dd, J 10.5, 10.5 Hz,
CHCHaHbN); δC (125 MHz, DMSO-d6) 154.0, 153.4, 145.1,
138.8, 130.1, 128.0, 118.5, 116.8, 113.5, 113.0, 110.8, 104.7,
81.1, 60.9, 57.0, 56.9, 55.6, 55.0, 49.7, 46.0, 43.8, 35.2; MS (EI)
m/z (%) 405 (100, M+), 390 (20), 340 (41), 305 (24), 181 (78).
isothiochromene-5,7,7(3H)-tricarbonitrile 6b. White solid, 80%;
m.p. 252−254 C: [Found: C, 65.39; H, 4.72; N, 16.22; S, 9.34.
o
C19H16N4OS requires C, 65.50; H, 4.63; N, 16.08; S, 9.20%]; νmax
(KBr) 3344, 2214, 1640, 1597 cm-1; δH (500 MHz, DMSO-d6)
7.51 (2H, ap s, Ar), 7.37 (2H, br s, NH2), 7.04 (2H, ap s, Ar),
5.95−5.93 (1H, m, =CH), 3.80 (3H, s, OMe), 3.61 (1H, d, J 12.0
Hz, CHAr), 3.45 (1H, ddd, J 18.0, 3.0, 3.0 Hz, =CHCHaHbS),
3.16 (1H, dd, J 18.5, 5.5 Hz, =CHCHaHbS), 2.97 (1H, ddd, J
12.0, 10.5, 4.5 Hz, CHCH2S), 2.31 (1H, dd, J 13.5, 4.5 Hz,
CHaHbS), 2.22 (1H, dd, J 13.5, 10.5 Hz, CHaHbS); δC (125 MHz,
DMSO-d6) 160.6, 144.9, 130.6, 126.4, 118.3, 116.9, 115.3,
113.2, 113.0, 82.4, 56.0, 49.8, 44.0, 36.2, 28.6, 25.9; MS (EI) m/z
(%) 348 (6, M+), 301 (82), 161 (78), 146 (47), 118 (100).
4.2.2.
6-Amino-2-methyl-8-(4-nitrophenyl)-2,3,8,8a-
tetrahydroisoquinoline-5,7,7(1H)-tricarbonitrile 5e. White solid,
o
77%; m.p. 181−184 C: [Found: C, 63.51; H, 4.58; N, 23.39.
C19H16N6O2 requires C, 63.32; H, 4.48; N, 23.32%]; νmax (KBr)
3354, 3084, 2212, 1726 cm-1; δH (500 MHz, DMSO-d6) 8.34 (1H,
d, J 8.0 Hz, Ar), 8.30 (1H, d, J 8.0 Hz, Ar), 7.92 (1H, d, J 8.0 Hz,
Ar), 7.70 (1H, d, J 8.0 Hz, Ar), 7.53 (2H, s, NH2), 5.66−5.65 (1H,
m, =CH), 3.94 (1H, d, J 12.5 Hz, CHAr), 3.33−3.29 (1H, m,
=CHCHaHbN), 3.06−3.03 (1H, m, CHCH2N), 2.61 (1H, ddd, J
18.0, 3.0, 3.0 Hz, =CHCHaHbN), 2.35 (1H, dd, J 11.0, 5.0 Hz,
CHCHaHbN), 2.09 (3H, s, NMe), 1.62 (1H, dd, J 10.5, 10.5 Hz,
CHCHaHbN); δC (125 MHz, DMSO-d6) 148.9, 144.6, 141.9,
134.5, 129.3, 127.5, 124.8, 124.6, 118.9, 116.6, 112.8, 112.7,
81.3, 55.5, 54.9, 48.4, 45.8, 43.0, 34.9; MS (EI) m/z (%) 360 (72,
M+), 332 (100), 201 (39), 159 (60), 136 (89).
4.2.7.
6-Amino-8-(3,4,5-trimethoxyphenyl)-8,8a-dihydro-1H-
isothiochromene-5,7,7(3H)-tricarbonitrile 6c. White solid, 79%;
m.p. 232−233 C: [Found: C, 61.79; H, 5.12; N, 13.91; S, 7.62.
o
C21H20N4O3S requires C, 61.75; H, 4.94; N, 13.72; S, 7.85%];
νmax (KBr) 3338, 2211, 1650, 1594 cm-1; δH (500 MHz, DMSO-
d6) 7.50 (2H, s, NH2), 6.87 (1H, s, Ar), 6.77 (1H, s, Ar),
5.92−5.91 (1H, m, =CH), 3.82 (3H, s, OMe), 3.78 (3H, s, OMe),
3.68 (3H, s, OMe), 3.52 (1H, d, J 12.0 Hz, CHAr), 3.38 (1H, ddd,
J 18.5, 3.0, 3.0 Hz, =CHCHaHbS), 3.12 (1H, dd, J 18.5, 5.5 Hz,
=CHCHaHbS), 2.97 (1H, ddd, J 12.0, 10.5, 3.0 Hz, CHCH2S),
2.38 (1H, dd, J 13.5, 3.0 Hz, CHCHaHbS), 2.24 (1H, dd, J 13.5,
10.5 Hz, CHCHaHbS); δC (125 MHz, DMSO-d6) 145.1, 138.8,
130.6, 130.2, 118.5, 116.9, 113.5, 112.9, 104.8, 82.3, 60.9, 56.9,
51.0, 43.8, 36.0, 28.6, 25.8; MS (EI) m/z (%) 408 (100, M+), 391
(16), 360 (17), 212 (79), 181 (34), 164 (18).
4.2.3.
6-Amino-8-(4-cyanophenyl)-2-methyl-2,3,8,8a-
tetrahydroisoquinoline-5,7,7(1H)-tricarbonitrile 5f. White solid,
o
77%; m.p. 211−214 C: [Found: C, 70.68; H, 4.68; N, 24.52.
C20H16N6 requires C, 70.57; H, 4.74; N, 24.69%]; νmax (KBr)
3383, 3127, 2244, 2206, 1661 cm-1; δH (400 MHz, DMSO-d6)
8.02 (1H, d, J 8.0 Hz, Ar), 7.96 (1H, d, J 8.0 Hz, Ar), 7.85 (1H,
d, J 8.0 Hz, Ar), 7.65 (1H, d, J 8.0 Hz, Ar), 7.56 (2H, s, NH2),
5.68−5.67 (1H, m, =CH), 3.86 (1H, d, J 12.0 Hz, CHAr),
3.33−3.29 (1H, m, =CHCHaHbN), 3.09−3.04 (1H, m, CHCH2N),
2.64 (1H, ddd, J 18.5, 3.0, 3.0 Hz, =CHCHaHbN), 2.35 (1H, dd, J
11.0, 5.0 Hz, CHCHaHbN), 2.12 (3H, s, NMe), 1.63 (1H, dd, J
10.5, 10.5 Hz, CHCHaHbN); δC (100 MHz, DMSO-d6) 144.2,
139.7, 133.6, 133.3, 133.1, 128.5, 127.1, 118.8, 118.4, 116.3,
112.7, 112.5, 112.3, 80.8, 55.1, 54.5, 48.2, 45.5, 42.6, 34.4; MS
(EI) m/z (%) 342 (100), 340 (16, M+), 307 (42), 279 (57), 244
(37).
4.2.8.
6-Amino-8-(4-chlorophenyl)-8,8a-dihydro-1H-
isothiochromene-5,7,7(3H)-tricarbonitrile 6d. White solid, 81%;
m.p. 289−292 C: [Found: C, 61.39; H, 3.92; N, 16.01; S, 8.93.
o
C18H13ClN4S requires C, 61.27; H, 3.71; N, 15.88; S, 9.09%];
νmax (KBr) 3346, 2210, 1640, 1598 cm-1; δH (400 MHz, DMSO-
d6) 7.68−7.47 (6H, m, Ar, NH2), 5.96−5.94 (1H, m, =CH), 3.75
(1H, d, J 12.0 Hz, CHAr), 3.44 (1H, ddd, J 18.0, 3.0, 3.0 Hz,
=CHCHaHbS), 3.15 (1H, dd, J 18.0, 6.0 Hz, =CHCHaHbS),
3.03−2.94 (1H, m, CHCH2S), 2.31−2.23 (2H, m, CH2S); δC (100
MHz, DMSO-d6) 144.4, 134.6, 133.3, 129.9, 129.5, 118.2, 116.4,
112.6, 112.4, 82.0, 49.2, 43.1, 35.4, 28.1, 25.4; (EI) m/z (%) 354
(30, M+2), 352 (93, M+), 294 (49), 227 (43), 151 (71), 125 (95).
4.2.4.
6-Amino-8-phenyl-8,8a-dihydro-1H-isothiochromene-
5,7,7(3H)-tricarbonitrile 6a. White solid, 78%; m.p. 281−283 oC:
[C, 67.81; H, 4.52; N, 17.81; S, 9.93. C18H14N4S requires C,
67.90; H, 4.43; N, 17.60; S, 10.07%]; νmax (KBr) 3331, 3164,
2208, 1668, 1604 cm-1; δH (400 MHz, DMSO-d6) 7.66−7.44 (7H,
m, Ph, NH2), 5.96−5.93 (1H, m, =CH), 3.66 (1H, d, J 12.0 Hz,
CHPh), 3.44 (1H, ddd, J 18.0, 3.0, 3.0 Hz, =CHCHaHbS), 3.17
(1H, ddd, J 18.0, 6.0, 1.0 Hz, =CHCHaHbS), 3.02−3.00 (1H, m,
CHCH2S), 2.27−2.25 (2H, m, CH2S); δC (100 MHz, DMSO-d6)
144.6, 134.3, 130.1, 129.7, 129.4, 118.1, 116.5, 112.7, 112.5,
82.0, 49.9, 43.3, 35.6, 28.2, 25.5; MS (EI) m/z (%) 318 (22, M+),
314 (32), 300 (21), 273 (8), 210 (28), 105 (100).
4.2.9.
6-Amino-8-(4-bromophenyl)-8,8a-dihydro-1H-
isothiochromene-5,7,7(3H)-tricarbonitrile 6h. White solid, 73%;
m.p. 294−297 C: [Found: C, 54.55; H, 3.43; N, 14.01; S, 8.21.
o
C18H13BrN4S requires C, 54.42; H, 3.30; N, 14.10; S, 8.07%];
νmax (KBr) 3346, 2210, 1641, 1598 cm-1; δH (400 MHz, DMSO-
d6) 7.70 (2H, d, J 8.0 Hz, Ar), 7.56 (2H, ap s, Ar), 7.41 (2H, br s,
NH2), 5.96−5.94 (1H, m, =CH), 3.76 (1H, d, J 12.0 Hz, CHAr),
3.45 (1H, ddd, J 18.0, 3.0, 3.0 Hz, =CHCHaHbS), 3.16 (1H, dd, J
18.0, 6.0 Hz, =CHCHaHbS), 3.02−2.99 (1H, m, CHCH2S),
2.31−2.20 (2H, m, CH2S); δC (100 MHz, DMSO-d6) 144.4, 133.7,
132.4, 129.9, 123.3, 118.2, 116.4, 112.6, 112.4, 82.0, 49.2, 43.1,
35.4, 28.1, 25.5; MS (EI) m/z (%) 398 (16, M+2), 396 (18, M+),
244 (29), 227 (18), 69 (100).
4.2.5.
6-Amino-8-(p-tolyl)-8,8a-dihydro-1H-isothiochromene-
5,7,7(3H)-tricarbonitrile 6g. White solid, 75%; m.p. 272−273 oC:
[Found: C, 68.49; H, 4.78; N, 17.09; S, 9.90. C19H16N4S requires
C, 68.65; H, 4.85; N, 16.85; S, 9.65%]; νmax (KBr) 3340, 3230,
2211, 1642 cm-1; δH (500 MHz, DMSO-d6) 7.48 (4H, ap s, Ar),
7.26 (2H, s, NH2), 5.90 (1H, ap s, =CH), 3.57 (1H, d, J 12.0 Hz,
CHAr), 3.42−3.38 (1H, m, =CHCHaHbS), 3.14−3.11 (1H, m,
=CHCHaHbS), 2.95−2.91 (1H, m, CHCH2S), 2.31 (3H, s, Me),
2.23−2.20 (2H, m, CH2S); δC (125 MHz, DMSO-d6) 145.1, 139.6,
131.7, 130.6, 130.4, 118.9, 118.4, 116.9, 113.2, 113.0, 82.4, 50.1,
43.9, 36.1, 28.6, 25.9, 21.6; MS (EI) m/z (%) 332 (100, M+), 299
(20), 274 (40), 131 (57), 105 (82).
4.2.10.
6-Amino-8-(4-nitrophenyl)-8,8a-dihydro-1H-
isothiochromene-5,7,7(3H)-tricarbonitrile 6e. White solid, 85%;
m.p. 255−258 C: [Found: C, 59.61; H, 3.75; N, 19.40; S, 8.71.
o
C18H13N5O2S requires C, 59.49; H, 3.61; N, 19.27; S, 8.82%];
νmax (KBr) 3341, 2212, 1600, 1515 cm-1; δH (500 MHz, DMSO-
d6) 8.32 (2H, d, J 8.5 Hz, Ar), 7.91 (1H, br s, Ar), 7.72 (1H, br s,
Ar), 7.55 (2H, s, NH2) 5.95−5.94 (1H, m, =CH), 3.96 (1H, d, J
12.0 Hz, CHAr), 3.40 (1H, ddd, J 18.5, 3.0, 3.0 Hz,
=CHCHaHbS), 3.14 (1H, dd, J 18.5, 6.0 Hz, =CHCHaHbS),
3.06−3.05 (1H, m, CHCH2S), 2.23−2.22 (2H, m, CH2S); δC (125