The Journal of Organic Chemistry
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(2C), 124.2, 125.5, 127.0, 127.6 (2C), 128.1, 128.4 (2C), 128.9, 129.4,
129.9 (2C), 130.9, 133.1, 134.6, 135.8, 144.0, 155.3; IR (ATR) ν 3420,
1510, 1335, 1265, 1154, 1013, 961, 838, 732, 670 cm−1; HRMS (ESI-
10-Cyclohexyl-4a-(4-methoxyphenyl)-5-(methylsulfonyl)-2-tosyl-
1,2,3,4,4a,5-hexahydrobenzo[b][1,6]naphthyridine (6g). This com-
pound was synthesized from 5g (131.6 mg, 0.210 mmol) according to
the general procedure and was obtained in 86% yield (110.0 mg).
White solid: mp 103−105 °C; Rf = 0.48 (n-hexane/EtOAc = 1/1); 1H
NMR (400 MHz, CDCl3, 55 °C) δ 1.34−1.47 (m, 3H), 1.67−1.96 (m,
7H), 2.44 (s, 3H), 2.52−2.58 (m, 1H), 2.59−2.66 (m, 1H), 2.71 (s,
3H), 2.76−2.80 (m, 1H), 2.86−2.94 (m, 1H), 3.37 (dd, J = 10.0, 5.2
Hz, 1H), 3.66 (s, 3H), 4.10 (d, J = 15.6 Hz, 1H), 4.72 (d, J = 15.6 Hz,
1H), 6.51−6.54 (m, 2H), 6.97 (t, J = 7.6 Hz, 1H), 7.02 (t, J = 7.6 Hz,
1H), 7.11 (br-s, 2H), 7.18 (d, J = 7.6 Hz, 1H), 7.31 (d, J = 7.6 Hz,
1H), 7.32 (d, J = 8.0 Hz, 2H), 7.67 (d, J = 8.0 Hz, 2H); 13C NMR
(100 MHz, CDCl3, 55 °C) δ 21.5, 26.1, 27.0, 27.4, 30.3, 31.9, 32.7,
40.1, 40.7, 41.0, 43.9, 55.1, 65.0, 113.3 (2C), 123.8, 126.5, 127.5 (2C),
127.6, 128.0, 129.8 (2C), 130.4 (2C), 132.0, 132.0, 132.0, 135.1, 135.9,
136.7, 143.7, 159.0; IR (ATR) ν 2928, 1507, 1337, 1249, 1155, 1105,
1024, 961, 815, 733 cm−1; HRMS (ESI-TOF) m/z [M + Na]+ Calcd
+
TOF) m/z [M + Na]+ Calcd for C26H26N2NaO5S2 533.1175, found
533.1191.
4a-(4-(Benzyloxy)phenyl)-5-(methylsulfonyl)-2-tosyl-1,2,3,4,4a,5-
hexahydrobenzo[b][1,6]naphthyridine (6c). This compound was
synthesized from 5c (134.3 mg, 0.217 mmol) according to the general
procedure and was obtained in 71% yield (93.0 mg). White solid: mp
1
95−98 °C; Rf = 0.50 (n-hexane/EtOAc = 1/1); H NMR (400 MHz,
CDCl3) δ 2.37 (td, J = 12.4, 2.2 Hz, 1H), 2.42 (s, 3H), 2.70−2.76 (m,
1H), 2.75 (s, 3H), 2.98−3.05 (m, 1H), 2.60−2.66 (m, 1H), 3.85 (d, J
= 14.8 Hz, 1H), 4.41 (d, J = 14.8 Hz, 1H), 4.89 (s, 2H), 6.69 (d, J =
8.4 Hz, 2H), 6.71 (s, 1H), 7.00−7.10 (m, 3H), 7.15 (d, J = 8.4 Hz,
2H), 7.21 (d, J = 8.4 Hz, 1H), 7.30−7.35 (m, 7H), 7.66 (d, J = 8.4 Hz,
2H); 13C NMR (100 MHz, CDCl3) δ 21.5, 35.2, 39.9, 42.8, 49.2, 65.4,
69.9, 114.3 (2C), 124.2, 125.4, 127.0, 127.5 (2C), 127.6 (2C), 128.0,
128.1, 128.3 (2C), 128.5 (2C), 128.9, 129.4, 129.9 (2C), 131.3, 133.4,
134.7, 135.9, 136.5, 143.9, 158.3; IR (ATR) ν 1605, 1506, 1338, 1244,
1156, 1013, 960, 835, 733, 698, 674 cm−1; HRMS (ESI-TOF) m/z [M
+
for C33H38N2NaO5S2 629.2114, found 629.2098.
4a-(4-Methoxyphenyl)-9-methyl-5-(methylsulfonyl)-2-tosyl-
1,2,3,4,4a,5-hexahydrobenzo[b][1,6]naphthyridine (6h). This com-
pound was synthesized from 5h (120.5 mg, 0.216 mmol) according to
the general procedure and was obtained in 73% yield (84.8 mg). White
solid: mp 120−122 °C; Rf = 0.47 (n-hexane/EtOAc = 1/1); 1H NMR
(400 MHz, CDCl3) δ 2.31 (s, 3H), 2.39 (td, J = 12.0, 2.4 Hz, 1H),
2.44 (s, 3H), 2.64 (br-dd, J = 12.0, 2.4 Hz, 1H), 2.76 (s, 3H), 3.02 (td,
J = 12.0, 2.8 Hz, 1H), 3.57−3.61 (m, 1H), 3.67 (s, 3H), 3.99 (dd, J =
14.8, 1.6 Hz, 1H), 4.38 (d, J = 14.8 Hz, 1H), 6.61 (d, J = 8.4 Hz, 2H),
6.89−6.95 (m, 3H), 7.04 (dd, J = 7.2, 2.4 Hz, 1H), 7.15 (d, J = 8.4 Hz,
2H), 7.33 (d, J = 8.0 Hz, 2H), 7.67 (d, J = 8.0 Hz, 2H); 13C NMR
(100 MHz, CDCl3) δ 18.8, 21.6, 34.9, 40.1, 42.7, 49.2, 55.1, 64.6,
113.4 (2C), 121.2, 127.4, 127.5, 127.6 (2C), 127.7, 128.1 (2C), 128.7,
129.9 (2C), 131.2, 133.0, 133.3, 134.8, 135.7, 143.9, 158.9; IR (ATR)
ν 1508, 1465, 1339, 1252, 1160, 1033, 962, 819, 735, 668 cm−1;
+
+ Na]+ Calcd for C33H32N2NaO5S2 623.1645, found 623.1642.
4a-(4-Methoxy-3-methylphenyl)-5-(methylsulfonyl)-2-tosyl-
1,2,3,4,4a,5-hexahydrobenzo[b][1,6]naphthyridine (6d). This com-
pound was synthesized from 5d (93.0 mg, 0.167 mmol) according to
the general procedure and was obtained in 73% yield (66.0 mg). White
solid: mp 132−134 °C; Rf = 0.46 (n-hexane/EtOAc = 1/1); 1H NMR
(400 MHz, CDCl3) δ 2.05 (s, 3H), 2.32−2.39 (m, 1H), 2.42 (s, 3H),
2.70−2.76 (m, 1H), 2.75 (s, 3H), 2.99 (td, J = 12.0, 4.8 Hz, 1H),
3.60−3.68 (m, 1H), 3.68 (s, 3H), 3.84 (d, J = 14.8 Hz, 1H), 4.42 (d, J
= 14.8 Hz, 1H), 6.44 (d, J = 8.0 Hz, 1H), 6.71 (s, 1H), 6.87 (d, J = 8.0
Hz, 1H), 7.00−7.09 (m, 4H), 7.20 (d, J = 8.0 Hz, 1H), 7.31 (d, J = 8.0
Hz, 2H), 7.66 (d, J = 8.0 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ
16.3, 21.5, 35.2, 39.9, 42.8, 49.3, 55.1, 65.5, 108.8, 124.1, 125.4, 125.4,
126.6, 126.9, 127.6 (2C), 128.0, 129.0, 129.3, 129.5, 129.8 (2C), 130.4,
133.5, 134.8, 136.0, 143.8, 157.2; IR (ATR) ν 1501, 1338, 1249, 1157,
1100, 1029, 960, 814, 733 cm−1; HRMS (ESI-TOF) m/z [M + Na]+
+
HRMS (ESI-TOF) m/z [M + Na]+ Calcd for C28H30N2NaO5S2
561.1488, found 561.1503.
8-Chloro-4a-(4-methoxyphenyl)-5-(methylsulfonyl)-2-tosyl-
1,2,3,4,4a,5-hexahydrobenzo[b][1,6]naphthyridine (6i). This com-
pound was synthesized from 5i (55.2 mg, 0.096 mmol) according to
the general procedure and was obtained in 77% yield (41.2 mg). White
solid: mp 145−146 °C; Rf = 0.49 (n-hexane/EtOAc = 1/1); 1H NMR
(400 MHz, CDCl3) δ 2.35 (td, J = 12.6, 2.0 Hz, 1H), 2.43 (s, 3H),
2.71−2.75 (m, 1H), 2.77 (s, 3H), 3.00 (td, J = 12.6, 4.4 Hz, 1H),
3.63−3.66 (m, 1H), 3.68 (s, 3H), 3.86 (d, J = 15.2 Hz, 1H), 4.42 (d, J
= 15.2 Hz, 1H), 6.62 (d, J = 8.4 Hz, 2H), 6.66 (s, 1H), 6.99 (d, J = 8.4
Hz, 2H), 7.10−7.14 (m, 3H), 7.32 (d, J = 8.4 Hz, 2H), 7.66 (d, J = 8.4
Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 21.5, 35.1, 40.1, 42.7, 49.1,
55.1, 65.4, 113.5 (2C), 123.1, 125.0, 127.5 (2C), 128.0, 128.1 (2C),
129.9 (2C), 130.2, 130.5, 130.8, 132.5, 133.2, 133.2, 137.7, 144.0,
159.0; IR (ATR) ν 1508, 1338, 1252, 1158, 1027, 961, 803, 733, 659
+
Calcd for C28H30N2NaO5S2 561.1488, found 561.1496.
4a-(4-Methoxyphenyl)-10-methyl-5-(methylsulfonyl)-2-tosyl-
1,2,3,4,4a,5-hexahydrobenzo[b][1,6]naphthyridine (6e). This com-
pound was synthesized from 5e (143.0 mg, 0.257 mmol) according to
the general procedure and was obtained in 99% yield (137.1 mg).
White solid: mp 130−132 °C; Rf = 0.55 (n-hexane/EtOAc = 1/1); 1H
NMR (400 MHz, CDCl3, 55 °C) δ 2.22 (s, 3H), 2.43 (s, 3H), 2.45−
2.57 (m, 2H), 2.68 (s, 3H), 2.98 (td, J = 13.0, 5.6 Hz, 1H), 3.48−3.53
(m, 1H), 3.65 (s, 3H), 4.33 (s, 2H), 6.54 (d, J = 8.0 Hz, 2H), 6.99−
7.09 (m, 4H), 7.19 (d, J = 8.0 Hz, 2H), 7.31 (d, J = 8.0 Hz, 2H), 7.67
(d, J = 8.0 Hz, 2H); 13C NMR (100 MHz, CDCl3, 55 °C) δ 13.5, 21.5,
34.1, 39.8, 41.6, 45.0, 55.0, 65.0, 113.3 (2C), 122.8, 127.0, 127.5 (2C),
127.7, 128.1, 128.2, 129.8 (2C), 130.0 (2C), 130.9, 132.0, 132.5, 134.6,
135.2, 143.7, 159.0; IR (ATR) ν 1606, 1507, 1335, 1249, 1155, 1104,
1034, 956, 959, 815, 734, 662 cm−1; HRMS (ESI-TOF) m/z [M +
cm−1
; HRMS (ESI-TOF) m/z [M +
Na]+ Calcd for
+
C27H27ClN2NaO5S2 581.0942, found 581.0962.
+
Na]+ Calcd for C28H30N2NaO5S2 561.1488, found 561.1492.
7-Chloro-4a-(4-methoxyphenyl)-5-(methylsulfonyl)-2-tosyl-
1,2,3,4,4a,5-hexahydrobenzo[b][1,6]naphthyridine (6j). This com-
pound was synthesized from 5j (106.2 mg, 0.184 mmol) according to
the general procedure and was obtained in 76% yield (78.2 mg). White
solid: mp 184−187 °C; Rf = 0.42 (n-hexane/EtOAc = 1/1); 1H NMR
(400 MHz, CDCl3) δ 2.36 (td, J = 12.8, 3.0 Hz, 1H), 2.43 (s, 3H),
2.72−2.77 (m, 1H), 2.77 (s, 3H), 2.98 (td, J = 12.8, 4.8 Hz, 1H),
3.62−3.67 (m, 1H), 3.70 (s, 3H), 3.83 (d, J = 14.8 Hz, 1H), 4.39 (d, J
= 14.8 Hz, 1H), 6.64 (d, J = 8.4 Hz, 2H), 6.68 (s, 1H), 6.95 (d, J = 8.0
Hz, 1H), 7.05 (dd, J = 8.0, 2.0 Hz, 1H), 7.12 (d, J = 8.4 Hz, 2H), 7.24
(d, J = 2.0 Hz, 1H), 7.32 (d, J = 8.4 Hz, 2H), 7.65 (d, J = 8.4 Hz, 2H);
13C NMR (100 MHz, CDCl3) δ 21.5, 35.3, 40.2, 42.7, 49.2, 55.1, 65.6,
4a-(4-Methoxyphenyl)-5-(methylsulfonyl)-10-pentyl-2-tosyl-
1,2,3,4,4a,5-hexahydrobenzo[b][1,6]naphthyridine (6f). This com-
pound was synthesized from 5f (152.9 mg, 0.250 mmol) according to
the general procedure and was obtained in 70% yield (103.8 mg).
White solid: mp 166−169 °C; Rf = 0.56 (n-hexane/EtOAc = 1/1); 1H
NMR (400 MHz, CDCl3, 55 °C) δ 0.95 (t, J = 7.6 Hz, 3H), 1.38−1.60
(m, 6H), 2.44 (s, 3H), 2.52−2.59 (m, 3H), 2.61−2.70 (m, 1H), 2.70
(s, 3H), 2.93−3.00 (m, 1H), 3.48 (dd, J = 9.6, 4.0 Hz, 1H), 3.65 (s,
3H), 4.26 (d, J = 16.0 Hz, 1H), 4.45 (d, J = 16.0 Hz, 1H), 6.54 (d, J =
8.8 Hz, 2H), 7.01 (td, J = 8.0, 0.8 Hz, 1H), 7.03−7.14 (m, 3H), 7.20
(dd, J = 8.0, 0.8 Hz, 1H), 7.22 (dd, J = 8.0, 0.8 Hz, 1H), 7.31 (d, J =
8.0 Hz, 2H), 7.68 (d, J = 8.0 Hz, 2H); 13C NMR (100 MHz, CDCl3,
55 °C) δ 13.9, 21.5, 22.4, 27.8, 28.7, 32.3, 33.9, 40.2, 41.5, 44.4, 55.1,
64.7, 113.3 (2C), 122.7, 126.9, 127.5 (2C), 127.7, 128.1, 129.8 (2C),
130.3 (2C), 130.6, 131.0, 132.6, 133.3, 134.8, 135.6, 143.6, 159.0; IR
(ATR) ν 2918, 1507, 1336, 1249, 1156, 1104, 1034, 959, 815, 735, 660
113.6 (2C), 123.2, 126.2, 127.1, 127.3, 127.6 (2C), 128.2 (2C), 129.2,
129.9 (2C), 130.5, 133.2, 133.2, 135.8, 136.2, 144.0, 159.1; IR (ATR)
ν 1596, 1508, 1340, 1253, 1159, 1105, 1027, 960, 817, 735, 666 cm−1;
+
HRMS (ESI-TOF) m/z [M + Na]+ Calcd for C27H27ClN2NaO5S2
581.0942, found 581.0962.
4a-(4-Methoxyphenyl)-6-methyl-5-(methylsulfonyl)-2-tosyl-
1,2,3,4,4a,5-hexahydrobenzo[b][1,6]naphthyridine (6k). This com-
cm−1
; HRMS (ESI-TOF) m/z [M +
Na]+ Calcd for
+
C32H38N2NaO5S2 617.2114, found 617.2128.
3873
dx.doi.org/10.1021/jo500308y | J. Org. Chem. 2014, 79, 3866−3875