Kumpaty et al.
(500 MHz, CDCl3): δ 8.41 (s, 1H), 8.20 (d, J ) 8.2 Hz, 1H), 7.87
(d, J ) 7.8 Hz, 1H), 7.59 (d, J ) 8.7 Hz, 1H), 7.57 (d, J ) 8.0 Hz,
1H), 7.47 (s, 1H), 7.39-7.27 (m, 5H), 7.28 (d, J ) 7.6 Hz, 1H),
7.23-7.18 (m, 2H), 5.64 (s, 1H), 4.23-4.18 (m, 1H), 4.15-4.12
(m, 1H), 4.05 (d, J ) 13.8 Hz, 1H), 4.00 (t, J ) 4.7 Hz, 1H), 3.83
(d, J ) 13.8 Hz, 1H), 3.31 (d, J ) 4.8 Hz, 2H), 1.26 (t, J ) 7.1
Hz, 3H). 13C NMR (125 MHz, CDCl3): δ 172.8, 149.1, 145.4, 139.2,
137.1, 135.2, 133.7, 130.2, 129.0, 127.8, 127.3, 124.1, 123.6, 122.6,
120.1, 118.9, 111.4, 107.7, 60.9, 56.8, 55.2, 24.8, 14.7. MS (EI)
m/e (rel intensity): 455 (M+, 26), 382 (63), 364 (100), 217 (51).
Anal. Calcd for C27H25N3O4: C, 71.19; H, 5.53; N, 9.22. Found: C,
71.16; H, 5.52; N, 8.83.
cis-1-(4-Chlorophenyl)-2,3,4,9-tetrahydro-1H-ꢀ-carboline-3-
carboxylic Acid Ethyl Ester (2c). The general procedure was
followed. L-Tryptophan ethyl ester (13.5 g, 0.058 mol), 4-chlo-
robenzaldehyde (9.4 g, 0.067 mol), and TFA (13.2 g, 0.12 mol)
were used to obtain the product. Mp: 140-142 °C. 1H NMR (500
MHz, CDCl3): δ 7.61 (d, J ) 7.6 Hz, 1H), 7.42 (s, 1H), 7.41 (s,
3H), 7.32 (s, 1H), 7.28 (d, J ) 7.8 Hz, 1H), 7.23-7.17 (m, 2H),
5.29 (s, 1H), 4.38-4.31 (m, 2H), 4.00 (dd, J ) 7.1, 4.1 Hz, 1H),
3.28 (dd, J ) 11.3, 3.8 Hz, 1H), 3.08-3.03 (m, 1H), 2.42 (br s,
1H), 1.41 (t, J ) 7.1 Hz, 3H). 13C NMR (125 MHz, CDCl3): δ
173.1, 139.8, 136.7, 134.9, 134.6, 130.4, 129.6, 127.5, 122.6, 120.2,
118.8, 111.4, 109.7, 61.7, 58.5, 57.3, 26.1, 14.7. MS (EI) m/e (rel
intensity): 354 (M+, 50), 281 (84), 253 (67), 218 (100), 169 (42),
144, (63). Anal. Calcd for C20H19ClN2O2: C, 67.70; H, 5.40; N,
7.89. Found: C, 67.75; H, 5.35; N, 7.75. HRMS calcd for
C20H19ClN2O2 (M + H)+ 355.1213; found, 355.1217. The product
was used directly in a following step.
trans-1-(4-Chlorophenyl)-2,3,4,9-tetrahydro-1H-ꢀ-carboline-
3-carboxylic Acid Ethyl Ester (3c). The general procedure was
followed. L-Tryptophan ethyl ester (13.5 g, 0.058 mol), 4-chlo-
robenzaldehyde (9.4 g, 0.067 mol), and TFA (13.2 g, 0.12 mol)
were used to obtain the product. Mp: 152 °C. 1H NMR (500 MHz,
CDCl3): δ 7.73 (d, J ) 5.0 Hz, 1H), 7.63 (d, J ) 7.4 Hz, 1H), 7.36
(d, J ) 8.4 Hz, 2H), 7.30-7.20 (m, 5H), 5.43 (s, 1H), 4.26-4.22
(m, 2H), 3.96 (t, J ) 6.6 Hz, 1H), 3.25 (dd, J ) 5.4, 1.0 Hz, 1H),
3.20-3.18 (m, 1H), 2.42 (br s, 1H), 1.33 (t, J ) 7.1 Hz, 3H). 13C
NMR (125 MHz, CDCl3): δ 174.0, 141.7, 136.7, 134.4, 133.2,
130.2, 129.3, 127.4, 122.6, 120.1, 118.8, 111.4, 109.1, 61.6, 54.7,
52.9, 25.1, 14.6. MS (EI) m/e (rel intensity): 354 (M+, 74), 281
(84), 253 (27), 217 (100), 169 (44), 144 (64). HRMS calcd for
C20H19ClN2O2 (M + H)+ 355.1213; found, 355.1221. The product
was used directly in a following step.
(m, 2H), 3.87 (d, J ) 13.8 Hz, 1H), 3.28-3.26 (m, 2H), 1.26 (t, J
) 7.1 Hz, 3H). 13C NMR (125 MHz, CDCl3): δ 173.4, 141.3, 139.7,
137.0, 134.8, 134.2, 130.7, 129.4, 129.0, 128.9, 127.7, 127.5, 122.3,
119.9, 118.7, 111.3, 107.2, 60.8, 56.5, 54.8, 24.8, 14.7. MS (EI)
m/e (rel intensity): 444 (M+, 63), 371, (85), 353 (100), 279 (34),
254 (49), 217 (91). HRMS calcd for C27H25ClN2O2 (M + H)+
444.1605; found, 444.1509.
cis-1-(4-Methylphenyl)-2,3,4,9-tetrahydro-1H-ꢀ-carboline-3-
carboxylic Acid Ethyl Ester (2d). The general procedure was
followed. L-Tryptophan ethyl ester (18.0 g, 0.077 mol), 4-methyl-
benzaldehyde (10.7 g, 0.089 mol), and TFA (17.6 g, 0.15 mol)
were used to obtain the product. Mp: 230-235 °C. 1H NMR (500
MHz, CDCl3): δ 7.60 (d, J ) 8.2 Hz, 1H), 7.47 (s, 1H), 7.34-7.32
(m, 2H), 7.27-7.24 (m, 3H), 7.21-7.16 (m, 2H), 5.27 (s, 1H),
4.36-4.30 (m, 2H), 4.01 (dd, J ) 11.0, 4.2 Hz, 1H), 3.28 (dd, J )
15.0, 4.2 Hz, 1H), 3.09-3.03 (m, 1H), 2.45 (s, 3H), 2.30 (br s,
1H), 1.40 (t, J ) 7.2 Hz, 3H). 13C NMR (125 MHz, CDCl3): δ
173.2, 138.8, 138.2, 136.6, 135.4, 130.0, 129.0, 127.7, 122.3, 120.0,
118.7, 111.3, 109.3, 61.6, 58.7, 57.5, 26.2, 21.6, 14.7. MS (EI)
m/e (rel intensity): 334 (M+, 100), 305 (26), 261 (93), 233 (74),
218 (88), 169 (36), 144 (41). Anal. Calcd for C21H22N2O2: C, 75.42;
H, 6.63; N, 8.38. Found: C, 75.31; H, 6.52; N, 8.02. HRMS calcd
for C21H22N2O2 (M + H)+ 335.1760; found, 335.1756. The product
was used directly in a following step.
trans-1-(4-Methylphenyl)-2,3,4,9-tetrahydro-1H-ꢀ-carboline-
3-carboxylic Acid Ethyl Ester (3d). The general procedure was
followed. L-Tryptophan ethyl ester (18.0 g, 0.077 mol), 4-methyl-
benzaldehyde (10.7 g, 0.089 mol), and TFA (17.6 g, 0.15 mol)
were used to obtain the product. Mp: 174 °C. [R]2D8: -48.19 (c 2.00,
CHCl3). 1H NMR (500 MHz, CDCl3): δ 7.62-7.59 (m, 2H), 7.29
(d, J ) 7.6 Hz, 1H), 7.23-7.17 (m, 6H), 5.45 (s, 1H), 4.27-4.20
(m, 2H), 4.01 (t, J ) 6.7 Hz, 1H), 3.32 (dd, J ) 15.4, 4.8 Hz, 1H),
3.18 (dd, J ) 15.4, 7.6 Hz, 1H), 2.58 (br s, 1H), 2.40 (s, 3H), 1.33
(t, J ) 6.6 Hz, 3H). 13C NMR (125 MHz, CDCl3): δ 174.1, 139.6,
138.3, 136.6, 133.9, 129.8, 128.7, 127.6, 122.3, 119.9, 118.7, 111.3,
108.9, 61.4, 55.2, 53.0, 25.1, 21.5, 14.6. MS (EI) m/e (rel intensity):
334 (M+, 100), 305 (48), 261 (85), 246 (28), 232 (42), 218 (85),
169 (38), 144 (36). Anal. Calcd for C21H22N2O2: C, 75.42; H, 6.63;
N, 8.83. Found: C, 75.21; H, 6.61; N, 8.17.
cis-2-Benzyl-1-(4-methylphenyl)-2,3,4,9-tetrahydro-1H-ꢀ-car-
boline-3-carboxylic Acid Ethyl Ester (4d). The general procedure
was followed. 2d (1.1 g, 3.3 mmol), DIPEA (0.6 g, 4.6 mmol),
and benzyl bromide (0.66 g, 3.9 mmol) were used to obtain the
1
product. Mp: 149-150 °C. H NMR (500 MHz, CDCl3): δ 7.58
cis-2-Benzyl-1-(4-chlorophenyl)-2,3,4,9-tetrahydro-1H-ꢀ-car-
boline-3-carboxylic Acid Ethyl Ester (4c). The general procedure
was followed. 2c (1.5 g, 4.2 mmol), DIPEA (0.81 g, 6.2 mmol),
and benzyl bromide (0.86 g, 5.0 mmol) were used to obtain the
product. Mp: 156 °C. [R]2D8: +66.92 (c 1.04, CHCl3). 1H NMR (500
MHz, CDCl3): δ 7.60 (d, J ) 8.2 Hz, 1H), 7.38-7.28 (m, 10H),
7.26 (d, J ) 7.2 Hz, 1H), 7.22-7.16 (m, 2H), 4.98 (s, 1H), 4.10
(d, J ) 14.8 Hz, 1H), 3.97 (d, J ) 14.8 Hz, 1H), 3.92-3.88 (m,
2H), 3.82-3.78 (m, 1H), 3.42 (dd, J ) 16.4, 3.0 Hz, 1H), 3.13
(dd, J ) 16.0, 5.2 Hz, 1H), 1.18 (t, J ) 7.2 Hz, 3H). 13C NMR
(125 MHz, CDCl3): δ 173.6, 139.3, 138.4, 136.8, 134.2, 133.1,
131.1, 129.6, 129.0, 128.6, 127.6, 127.2, 122.5, 120.1, 118.9, 111.2,
108.0, 61.30, 61.28, 61.1, 57.6, 24.3, 14.3. MS (EI) m/e (rel
intensity): 444 (M+, 38), 371 (100), 337 (23), 254 (40), 218 (53).
Anal. Calcd for C27H25ClN2O2: C, 72.88; H, 5.66; N, 6.30. Found:
C, 73.01; H, 5.80; N, 6.26. HRMS calcd for C27H25ClN2O2 (M +
H)+ 455.1683; found, 445.1665.
(d, J ) 7.4 Hz, 1H), 7.38-7.25 (m, 8H), 7.23 (d, J ) 6.6 Hz, 1H),
7.20-7.14 (m, 4H), 4.97 (s, 1H), 4.13 (d, J ) 14.9 Hz, 1H), 3.96
(d, J ) 14.9 Hz, 1H), 3.89-3.81 (m, 3H), 3.42 (dd, J ) 14.4, 7.6
Hz, 1H), 3.11 (dd, J ) 15.2, 4.8 Hz, 1H), 2.40 (s, 3H), 1.17 (t, J
) 7.2 Hz, 3H). 13C NMR (125 MHz, CDCl3): δ 173.7, 138.6, 138.2,
137.6, 136.8, 134.2, 129.7, 129.6, 128.4, 127.43, 127.36, 122.1,
119.9, 118.7, 111.2, 107.5, 62.1, 61.7, 61.0, 57.0, 24.9, 21.6, 14.3.
MS (EI) m/e (rel intensity): 424 (M+, 26), 351 (100), 259 (21),
234 (47), 218 (57). HRMS calcd for C28H28N2O2 (M + H)+
424.2151; found, 424.2149.
trans-2-Benzyl-1-(4-methylphenyl)-2,3,4,9-tetrahydro-1H-ꢀ-
carboline-3-carboxylic Acid Ethyl Ester (5d). The general
procedure was followed. 3d (4.0 g, 0.012 mol), DIPEA (2.3 g, 0.018
mol), and benzyl bromide (2.4 g, 0.014 mol) were used to obtain
the product. Mp: 174 °C. [R]2D8: -48.19 (c 2.00, CHCl3). 1H NMR
(500 MHz, CDCl3): δ 7.57 (d, J ) 6.8 Hz, 1H), 7.41 (d, J ) 8.0
Hz, 2H), 7.40 (s, 1H), 7.37-7.34 (m, 4H), 7.31-7.29 (m, 1H),
7.25-7.20 (m, 3H), 7.19-7.13 (m, 2H), 5.50 (s, 1H), 4.21-4.18
(m, 1H), 4.14-4.10 (m, 1H), 3.99 (t, J ) 4.8 Hz, 1H), 3.97 (d, J
) 13.8 Hz, 1H), 3.92 (d, J ) 13.9 Hz, 1H), 3.27 (d, J ) 6.4 Hz,
2H), 2.40 (s, 3H), 1.26 (t, J ) 7.1 Hz, 3H). 13C NMR (125 MHz,
CDCl3): δ 173.6, 140.1, 139.6, 138.2, 136.9, 135.7, 129.9, 129.3,
129.0, 128.8, 127.6, 127.5, 121.9, 119.7, 118.6, 111.2, 106.8, 61.1,
60.6, 56.5, 54.7, 24.9, 21.6, 14.7. MS (EI) m/e (rel intensity): 424
(M+, 78), 351 (93), 333 (100), 259 (41), 234 (36), 218 (67). Anal.
trans-2-Benzyl-1-(4-chlorophenyl)-2,3,4,9-tetrahydro-1H-ꢀ-
carboline-3-carboxylic Acid Ethyl Ester (5c). The general
procedure was followed. 3c (0.63 g, 1.8 mmol), DIPEA (0.34 g,
2.7 mmol), and benzyl bromide (0.36 g, 2.1 mmol) were used to
1
obtain the product. Mp: 172 °C. H NMR (500 MHz, CDCl3): δ
7.59 (d, J ) 7.4 Hz, 1H), 7.46 (d, J ) 8.4 Hz, 2H), 7.43 (s, 1H),
7.39-7.29 (m, 7H), 7.27 (d, J ) 7.4 Hz, 1H), 7.21-7.15 (m, 2H),
5.51 (s, 1H), 4.22-4.17 (m, 1H), 4.14-4.11 (m, 1H), 4.00-3.98
2778 J. Org. Chem. Vol. 74, No. 7, 2009