X.-L. Liu et al. / Tetrahedron 71 (2015) 9483e9495
9493
(m, 1H), 7.07e7.15 (m, 2H); 13C NMR (CDCl3, 100 MHz)
d: 21.3, 29.9,
6.99e7.12 (m, 2H); 13C NMR (CDCl3, 100 MHz)
d: 29.9, 32.1, 34.8,
31.6, 34.6, 34.8, 47.4, 49.9, 86.9, 106.6, 118.2, 123.0, 127.4, 127.8,
128.6, 131.1, 132.0, 136.4, 137.5, 150.9, 173.6; HRMS (ESI-TOF) m/z:
Calcd for C21H24N2NaO [MþNa]þ: 343.1786; Found: 343.1786.
35.0, 39.4, 50.5, 55.9, 56,0, 56.1, 86.5, 96.9, 106.8, 115.1, 116.5, 118.0,
122.9, 128.5, 132.0, 142.1, 147.9, 151.4, 151.5, 173.5; HRMS (ESI-TOF)
m/z: Calcd for C23H28N2NaO4 [MþNa]þ: 419.1946; Found: 419.1948.
4.3.14. 4a-(2-Methoxybenzyl)-1,9-dimethyl-4,4a,9,9a-tetrahydro-
4.3.20. 1,9-Dimethyl-4a-(2,3,4-trimethoxybenzyl)-4,4a,9,9a-tetrahy-
1H-pyrido[2,3-b]indol-2(3H)-one
(4n). White
powder,
mp
dro-1H-pyrido[2,3-b]indol-2(3H)-one (4t). White powder, mp
124.6e125.5 ꢁC; Overall yield 60%; 1H NMR (CDCl3, 400 MHz)
d:
150.4e151.4 ꢁC; Overall yield 63%; 1H NMR (CDCl3, 400 MHz)
d:
2.01e2.25 (m, 4H), 2.70 (s, 3H), 2.87e2.95 (m, 4H), 3.10e3.19 (m,
1H), 3.78 (s, 3H), 4.77 (s, 1H), 6.30e6.35 (m, 1H), 6.69e6.79 (m, 3H),
6.83e6.88 (m, 1H), 6.95e7.00 (m, 1H), 7.07e7.13 (m, 1H), 7.14e7.27
2.08e2.28 (m, 4H), 2.76 (s, 3H), 2.89e2.94 (m, 1H), 2.98e3.03 (m,
4H), 3.83e3.86 (m, 6H), 3.89 (s, 3H), 4.88 (s, 1H), 6.35e6.38 (m, 1H),
6.46e6.53 (m, 2H), 6.75e6.81 (m, 1H), 7.01e7.05 (m, 1H), 7.12e7.17
(m, 1H); 13C NMR (CDCl3, 100 MHz)
d: 30.0, 31.7, 34.7, 34.9, 39.8,
(m, 1H); 13C NMR (CDCl3, 100 MHz)
d: 24.1, 30.0, 31.8, 34.9, 40.0,
50.3, 55.1, 87.0, 106.5, 110.4, 118.1, 120.2, 123.2, 128.0, 128.4, 132.1,
50.4, 55.9, 60.8, 64.3, 86.7, 106.8, 118.2, 122.5, 122.9, 126.2, 128.6,
132.6, 150.8, 157.5, 173.8; HRMS (ESI-TOF) m/z: Calcd for
C
132.6,142.1,150.9,152.2,152.5,174.1; HRMS (ESI-TOF) m/z: Calcd for
C
21H24N2NaO2 [MþNa]þ: 359.1735; Found: 359.1739.
23H28N2NaO4 [MþNa]þ: 419.1946; Found: 419.1950.
4.3.15. 4a-(4-Methoxybenzyl)-1,9-dimethyl-4,4a,9,9a-tetrahydro-
4.3.21. 4a-(2,5-Dimethoxybenzyl)-1,9-dimethyl-4,4a,9,9a-tetrahy-
1H-pyrido[2,3-b]indol-2(3H)-one (4o). Pale yellow oil; Overall yield
dro-1H-pyrido[2,3-b]indol-2(3H)-one (4u). Pale yellow oil; Overall
61%; 1H NMR (CDCl3, 400 MHz)
d: 1.97e2.31 (m, 4H), 2.66 (s, 3H),
yield 57%; 1H NMR (CDCl3, 400 MHz)
d: 2.06e2.27 (m, 4H), 2.63 (s,
2.80e2.88 (m, 1H), 2.91e3.00 (m, 4H), 3.76 (s, 3H), 4.61 (s, 1H), 6.32
(d, J¼7.8 Hz, 1H), 6.69e6.77 (m, 3H), 6.78e6.85 (m, 2H), 6.90 (dd,
3H), 2.81e2.86 (m, 1H), 2.97 (s, 3H), 3.13e3.18 (m, 1H), 3.53 (s, 3H),
3.77 (s, 3H), 4.74 (s, 1H), 6.18e6.20 (m, 1H), 6.28e6.32 (m, 1H),
6.66e6.70 (m, 1H), 6.73e6.80 (m, 2H), 7.00e7.04 (m, 1H), 7.08e7.12
J¼0.9, 7.4 Hz, 1H), 7.08e7.28 (m, 1H); 13C NMR (CDCl3, 100 MHz)
d:
29.9, 31.8, 34.7, 34.9, 46.5, 50.0, 55.1, 87.0, 106.6, 113.3, 118.1, 123.0,
128.6, 131.2, 131.9, 150.9, 158.4, 173.6; HRMS (ESI-TOF) m/z: Calcd
for C21H24N2NaO2 [MþNa]þ: 359.1735; Found: 359.1736.
(m, 1H); 13C NMR (CDCl3, 100 MHz)
d: 30.0, 31.9, 34.8, 34.9, 40.0,
50.4, 55.4, 55.7, 86.7, 106.7, 111.4, 113.1, 117.2, 118.1, 122.9, 126.2,
128.5, 132.3, 151.1, 151.7, 152.8, 173.7. HRMS (ESI-TOF) m/z: Calcd for
C
22H26N2NaO3 [MþNa]þ: 389.1841; Found: 389.1843.
4.3.16. 4a-(2,3-Dimethoxybenzyl)-1,9-dimethyl-4,4a,9,9a-tetrahy-
dro-1H-pyrido[2,3-b]indol-2(3H)-one (4p). Pale yellow oil; Overall
4.3.22. 4a-(4-tert-Butylbenzyl)-1,9-dimethyl-4,4a,9,9a-tetrahydro-
yield 63%; 1H NMR (CDCl3, 400 MHz)
d: 2.07e2.24 (m, 4H), 2.70 (s,
1H-pyrido[2,3-b]indol-2(3H)-one (4v). Pale yellow oil; Overall yield
3H), 2.89e2.97 (m, 4H), 3.01e3.07 (m, 1H), 3.77 (s, 3H), 3.86 (s, 3H),
4.87 (s, 1H), 6.28e6.37 (m, 2H), 6.73e6.79 (m, 2H), 6.81e6.86 (m,
1H), 6.99e7.04 (m, 1H), 7.08e7.14 (m, 1H); 13C NMR (CDCl3,
56%; 1H NMR (CDCl3, 400 MHz)
d: 1.28 (s, 9H), 2.02e2.28 (m, 4H),
2.63 (s, 3H), 2.84e2.98 (m, 5H), 4.62 (s, 1H), 6.30e6.34 (m, 1H),
6.71e6.77 (m, 1H), 6.82e6.87 (m, 2H), 6.91e6.96 (m, 1H), 7.09e7.15
100 MHz)
d
: 29.9, 31.5, 34.7, 34.8, 39.9, 50.4, 55.6, 64.1, 86.4, 106.6,
(m, 1H), 7.20e7.27 (m, 2H); 13C NMR (CDCl3, 100 MHz)
d: 29.9, 31.3,
110.9, 118.1, 122.8, 123.3, 123.8, 128.5, 130.4, 132.5, 147.4, 150.8,
31.8, 34.3, 34.5, 34.7, 46.8, 49.9, 86.9,106.6,118.2,123.0,124.8,128.6,
129.9, 132.2, 133.4, 149.7, 150.8, 173.6; HRMS (ESI-TOF) m/z: Calcd
for C24H30N2NaO [MþNa]þ: 385.2255; Found: 385.2257.
152.7, 173.8; HRMS (ESI-TOF) m/z: Calcd for
[MþNa]þ: 389.1841; Found: 389.1846.
C22H26N2NaO3
4.3.17. 4a-(3,4-Dimethoxybenzyl)-1,9-dimethyl-4,4a,9,9a-tetrahy-
4.3.23. 4a-(4-Isopropylbenzyl)-1,9-dimethyl-4,4a,9,9a-tetrahydro-
dro-1H-pyrido[2,3-b]indol-2(3H)-one (4q). Pale yellow oil; Overall
1H-pyrido[2,3-b]indol-2(3H)-one
(4w). White
powder,
mp
d:
yield 62%; 1H NMR (CDCl3, 400 MHz)
d: 2.00e2.03 (m, 1H),
95.2e95.9 ꢁC; Overall yield 64%; 1H NMR (CDCl3, 400 MHz)
2.12e2.30 (m, 3H), 2.56 (s, 3H), 2.75e2.80 (m, 1H), 3.98e3.03 (m,
4H), 3.56 (s, 3H), 3.83 (s, 3H), 4.57 (s, 1H), 6.04e6.09 (m, 1H),
6.26e6.31 (m, 1H), 6.56e6.60 (m, 1H), 6.72e6.79 (m, 2H),
1.19e1.22 (m, 6H), 2.06e2.28 (m, 4H), 2.64 (s, 3H), 2.81e2.90 (m,
2H), 2.92 (s, 3H), 2.94e2.99 (m, 1H), 4.62 (s, 1H), 6.30e6.35 (m, 1H),
6.72e6.77 (m, 1H), 6.81e6.85 (m, 2H), 6.90e6.95 (m, 1H), 7.04e7.09
6.95e6.99 (m, 1H), 7.09e7.14 (m, 1H); 13C NMR (CDCl3, 100 MHz)
d:
(m, 2H), 7.10e7.15 (m, 1H); 13C NMR (CDCl3, 100 MHz)
d: 23.9, 24.0,
29.9, 32.1, 34.8, 34.9, 47.2, 50.2, 55.4, 55.8, 86.7, 106.9, 110.4, 113.0,
118.1,122.2,123.1,128.7,129.2,131.6,147.8,148.2,151.4,173.5; HRMS
(ESI-TOF) m/z: Calcd for C22H26N2NaO3 [MþNa]þ: 389.1841; Found:
389.1842.
29.9, 31.7, 33.6, 34.6, 34.8, 46.9, 49.9, 86.9, 106.6, 118.2, 123.0, 126.0,
128.6, 130.2, 132.2, 133.7, 147.4, 150.8, 173.6; HRMS (ESI-TOF) m/z:
Calcd for C23H28N2NaO [MþNa]þ: 371.2099; Found: 371.2097.
4.3.24. 4a-(3-Fluorobenzyl)-1,9-dimethyl-4,4a,9,9a-tetrahydro-1H-
4.3.18. 4a-(2,4-Dimethoxybenzyl)-1,9-dimethyl-4,4a,9,9a-tetrahy-
pyrido[2,3-b]indol-2(3H)-one (4x). White powder, mp 140.0e140.7
dro-1H-pyrido[2,3-b]indol-2(3H)-one (4r). Pale yellow oil; Overall
ꢁC; Overall yield 62%; 1H NMR (CDCl3, 400 MHz)
d: 2.05e2.30 (m,
yield 61%; 1H NMR (CDCl3, 400 MHz)
d: 1.99e2.21 (m, 4H), 2.72 (s,
4H), 2.64 (s, 3H), 2.87 (d, J¼13.4 Hz, 1H), 2.97 (s, 3H), 3.01 (d,
J¼13.4 Hz,1H), 4.59 (s,1H), 6.32 (d, J¼7.9 Hz,1H), 6.51e6.55 (m,1H),
6.68 (d, J¼7.7 Hz, 1H), 6.73e6.79 (m, 1H), 6.86e6.94 (m, 2H),
3H), 2.86 (d, J¼13.6 Hz,1H), 2.96 (s, 3H), 3.04 (d, J¼13.6 Hz,1H), 3.76
(s, 6H), 4.74 (s, 1H), 6.23e6.36 (m, 2H), 6.44 (d, J¼2.4 Hz, 1H), 6.67
(d, J¼8.3 Hz, 1H), 6.74 (dd, J¼0.8, 7.4 Hz, 1H), 6.96 (dd, J¼0.8, 7.3 Hz,
7.10e7.22 (m, 2H); 13C NMR (CDCl3, 100 MHz)
d: 29.7, 31.5, 34.6,
1H), 7.05e7.14 (m,1H); 13C NMR (CDCl3, 100 MHz)
d: 30.0, 31.7, 34.8,
34.8, 47.1, 49.9, 86.8, 106.7, 113.5, 116.8 (d, JCF¼21.1 Hz), 118.3, 122.9,
125.8 (d, JCF¼2.8 Hz), 128.9, 129.2, 138.9 (d, JCF¼7.2 Hz), 150.7, 162.3
(d, JCF¼244.5 Hz), 173.5; HRMS (ESI-TOF) m/z: Calcd for
35.0, 39.2, 50.3, 55.0, 55.2, 87.0, 98.3, 103.8, 106.5, 117.5, 118.0, 123.0,
132.5, 150.8, 158.4, 159.6, 173.9; HRMS (ESI-TOF) m/z: Calcd for
C
22H26N2NaO3 [MþNa]þ: 389.1841; Found: 389.1843.
C
20H21FN2NaO [MþNa]þ: 347.1535; Found: 347.1539.
4.3.19. 1,9-Dimethyl-4a-(2,4,5-trimethoxybenzyl)-4,4a,9,9a-tetrahy-
4.3.25. 1,9-Dimethyl-4a-(4-(trifluoromethyl)benzyl)-4,4a,9,9a-tetra-
hydro-1H-pyrido[2,3-b]indol-2(3H)-one (4y). Pale yellow oil; Over-
dro-1H-pyrido[2,3-b]indol-2(3H)-one (4s). White powder, mp
155.5e156.1 ꢁC; Overall yield 64%; 1H NMR (CDCl3, 400 MHz)
d:
all yield 63%; 1H NMR (CDCl3, 400 MHz)
d: 2.04e2.30 (m, 4H), 2.61
2.02e2.29 (m, 4H), 2.57 (s, 3H), 2.73e2.77 (m, 1H), 3.00 (s, 3H),
3.10e3.16 (m, 1H), 3.47 (s, 3H), 3.80 (s, 3H), 3.85 (s, 3H), 4.66 (s, 1H),
6.00 (s, 1H), 6.24e6.30 (m, 1H), 6.50 (s, 1H), 6.73e6.78 (m, 1H),
(s, 3H), 2.93 (d, J¼13.2 Hz, 1H), 2.98 (s, 3H), 3.08 (d, J¼13.3 Hz, 1H),
4.58 (d, J¼7.5 Hz, 1H), 6.31 (d, J¼7.8 Hz, 1H), 6.76 (t, J¼7.4 Hz, 1H),
6.85e7.00 (m, 3H), 7.11e7.15 (m, 1H), 7.42e7.56 (m, 2H); 13C NMR