The Journal of Organic Chemistry
ARTICLE
7.44-7.34 (m, 5 H), 7.15 (t, J = 8.0 Hz, 1 H), 7.10 (d, J = 8.5 Hz, 2 H),
6.85 (d, J = 8.5 Hz, 2 H), 6.75 (t, J = 7.0 Hz, 1 H), 4.45 (s, 2 H), 3.73 (s, 3
H), 2.56 (s, 3 H), 2.29 (s, 3 H); 13C NMR (125 MHz, CDCl3) δ 165.6,
148.7, 136.5, 135.0, 132.9, 130.6, 130.0, 128.3, 127.8, 127.3, 124.8, 123.0,
120.1, 119.8, 115.5, 113.0, 102.0, 50.8, 46.5, 37.0, 20.5; HRMS (EI) calcd
for C25H24N2O2 [M]þ 384.1838, found 384.1835.
Ethyl 3-((methyl(p-tolyl)amino)methyl)indolizine-1-carbox-
ylate (3h): 72% yield; white solid; 1H NMR (400 MHz, CD3SOCD3) δ
8.16 (d, J = 7.2 Hz, 1 H), 8.05 (d, J = 9.2 Hz, 1 H), 7.16 (t, J = 7.6 Hz, 1 H),
6.98 (d, J = 8.0 Hz, 2 H), 6.89-6.87 (m, 2 H), 6.80 (d, J = 7.6 Hz, 2 H), 4.69
(s, 2 H), 4.20 (q, J = 7.2 Hz, 2 H), 2.78 (s, 3 H), 2.16 (s, 3 H), 1.26 (t, J = 7.2
Hz, 3 H); 13C NMR (100 MHz, CD3SOCD3) δ 164.2, 147.9, 135.8, 130.0,
126.2, 125.3, 123.0, 122.7, 119.2, 115.5, 114.1, 112.9, 102.2, 59.3, 48.2, 38.4,
20.4, 14.9; HRMS (EI) calcd for C20H22N2O2 [M]þ 322.1681, found
322.1677.
7-Methyl-3-((methyl(phenyl)amino)methyl)indolizine-1-
carbonitrile (3o): 76% yield; white solid; 1H NMR (500 MHz,
CD3SOCD3) δ 8.13 (d, J = 7.0 Hz, 1 H), 7.43 (s, 1 H), 7.19 (t, J = 8.0
Hz, 2 H), 6.89 (s, 1 H), 6.88 (d, J = 9.0 Hz, 2 H), 6.79 (d, J = 7.5 Hz,
1 H), 6.70 (t, J = 7.0 Hz, 1 H), 4.74 (s, 2 H), 2.84 (s, 3 H), 2.34 (s, 3 H);
13C NMR (125 MHz, CD3SOCD3) δ 149.9, 138.7, 134.1, 129.5, 125.2,
122.8, 117.7, 117.6, 116.0, 115.9, 115.7, 114.0, 78.1, 47.8, 38.2, 21.0;
HRMS (EI) calcd for C18H17N3 [M]þ 275.1422, found 275.1430.
3-((Methyl(m-tolyl)amino)methyl)indolizine-1-carbonitrile
(3p): 70% yield; white solid; 1H NMR (400 MHz, CDCl3) δ 7.93 (d, J =
7.2 Hz, 1 H), 7.60 (d, J = 8.8 Hz, 1 H), 7.15 (t, J = 7.6 Hz, 1 H), 7.04 (t, J =
7.8 Hz, 1 H), 6.90 (s, 1 H), 6.73 (s, 1 H), 6.73-6.70 (m, 2 H), 6.65 (d, J =
7.6 Hz, 1 H), 4.56 (s, 2 H), 2.73 (s, 3 H), 2.31 (s, 3 H); 13C NMR (100
MHz, CDCl3) δ 150.1, 139.2, 138.7, 129.2, 124.5, 122.1, 122.0, 119.6,
117.9, 117.0, 116.9, 115.2, 113.0, 111.5, 80.8, 48.6, 37.5, 21.9; HRMS (EI)
calcd for C18H17N3 [M]þ 275.1422, found 275.1426.
3-(((4-Chlorophenyl)(methyl)amino)methyl)indolizine-1-
carbonitrile (3q): 86% yield; white solid; 1H NMR (400 MHz,
CD3SOCD3) δ 8.22 (d, J = 7.2 Hz, 1 H), 7.65 (d, J = 8.8 Hz, 1 H),
7.22-7.17 (m, 3 H), 6.96 (t, J = 7.2 Hz, 1 H), 6.94 (s, 1 H), 6.86 (d, J =
9.2 Hz, 2 H), 4.79 (s, 2 H), 2.88 (s, 3 H); 13C NMR (100 MHz,
CD3SOCD3) δ 148.5, 138.2, 129.1, 125.7, 123.3, 123.1, 121.1, 117.4,
117.2, 116.0, 115.1, 113.5, 79.7, 47.8, 38.4; HRMS (EI) calcd for
C17H14N3Cl [M]þ 295.0876, found 295.0890.
N,4-Dimethyl-N-((2-phenyl-1H-imidazol-5-yl)methyl)-
benzenamine (3i): 25% yield; white solid; H NMR (500 MHz,
1
CD3SOCD3) δ 12.4 (s, 1 H), 7.93 (d, J = 8.0 Hz, 2 H), 7.45 (t, J = 8.0 Hz,
2 H), 7.34 (t, J = 7.5 Hz, 1 H), 6.99 (d, J = 7.5 Hz, 2 H), 6.92 (s, 1 H), 6.75
(d, J = 7.5 Hz, 2 H), 4.43 (s, 2 H), 2.97 (s, 3 H), 2.19 (s, 3 H); 13C NMR
(125 MHz, CD3SOCD3) δ 147.8, 145.6, 139.9, 131.3, 129.8, 129.2, 128.3,
125.2, 124.7, 115.4, 113.3, 50.7, 38.9, 20.4; HRMS (EI) calcd for
C18H19N3 [M]þ 277.1579, found 277.1574.
N-(4-(Dimethylamino)benzyl)-N,4-dimethylbenzenamine
(3j):15 32% yield; light yellow solid; H NMR (400 MHz, CDCl3) δ
1
Methyl 3-(((4-ethylphenyl)(methyl)amino)methyl)indolizine-
1-carboxylate (3r): 73% yield; white solid; H NMR (400 MHz,
1
7.16 (d, J = 8.0 Hz, 2 H), 7.08 (d, J = 8.4 Hz, 2 H), 6.76 (t, J = 8.0 Hz, 4
H), 4.44 (s, 2 H), 2.97 (s, 9 H), 2.30 (s, 3 H); 13C NMR (100 MHz,
CDCl3) δ 149.7, 148.1, 129.6, 128.0, 126.9, 125.6, 113.0, 112.8, 56.5,
40.8, 38.3, 20.3; HRMS (EI) calcd for C17H22N2 [M]þ 254.1783, found
254.1787.
CD3SOCD3) δ 8.18 (d, J = 6.8 Hz, 1 H), 8.06 (d, J = 9.2 Hz, 1 H), 7.17
(t, J = 7.8 Hz, 1 H), 7.10 (d, J = 8.0 Hz, 2 H), 6.91 (s, 1 H), 6.90 (t, J =
6.4 Hz, 1 H), 6.80 (d, J =7.6 Hz, 2 H), 4.70 (s, 2 H), 3.73 (s, 3 H), 2.80 (s, 3
H), 2.46 (q, J = 7.6 Hz, 2 H), 1.10 (t, J = 7.6 Hz, 3 H); 13C NMR (100
MHz,CD3SOCD3) δ164.6, 148.0, 135.9, 132.9, 128.7, 125.3, 123.0, 122.7,
119.1, 115.5, 114.1, 113.0, 101.9, 51.0, 48.2, 38.5, 27.6, 16.3; HRMS (EI)
calcd for C20H22N2O2 [M]þ 322.1681, found 322.1682
Methyl 3-((methyl(phenyl)amino)methyl)indolizine-1-car-
boxylate (3s): 56% yield; white solid; 1H NMR (400 MHz,
CD3SOCD3) δ 8.19 (d, J = 7.2 Hz, 1 H), 8.07 (d, J = 9.2 Hz, 1 H),
7.21-7.16 (m, 3 H), 6.93-6.86 (m, 4 H), 6.68 (t, J = 7.2 Hz, 1 H), 4.78 (s,
2 H), 3.73 (s, 3 H), 2.88 (s, 3 H); 13C NMR (100 MHz, CD3SOCD3) δ
164.6, 149.8, 136.0, 129.5, 125.2, 123.0, 122.6, 119.1, 117.4, 115.3, 113.6,
113.0, 102.0, 51.0, 47.9, 38.2; HRMS (EI) calcd for C18H18N2O2 [M]þ
294.1368, found 294.1345.
3-(((4-Ethylphenyl)(methyl)amino)methyl)indolizine-1-car-
bonitrile (3k): 92% yield; white solid; H NMR (500 MHz, CD3-
1
SOCD3) δ 8.24 (d, J = 7.0 Hz, 1 H), 7.65 (d, J = 9.5 Hz, 1 H), 7.19 (t, J =
7.8 Hz, 1 H), 7.03 (d, J = 8.5 Hz, 2 H), 6.99 (s, 1 H), 6.95 (t, J = 6.5 Hz,
1 H), 6.83 (d, J = 8.5 Hz, 2 H), 4.71 (s, 2 H), 2.80 (s, 3 H), 2.48 (q, J = 7.6
Hz, 2 H), 1.11 (t, J = 7.5 Hz, 3 H); 13C NMR (100 MHz, CD3SOCD3) δ
148.0, 138.1, 133.2, 128.7, 125.8, 123.6, 123.2, 117.4, 117.2, 116.3, 114.4,
113.4, 79.6, 48.2, 38.6, 27.6, 16.3; HRMS (EI) calcd for C19H19N3 [M]þ
289.1579, found 289.1576.
3-(((4-tert-Butylphenyl)(methyl)amino)methyl)indolizine-
1-carbonitrile (3l): 90% yield; white solid; H NMR (500 MHz,
1
CD3SOCD3) δ 8.23 (d, J = 7.2 Hz, 1 H), 7.64 (d, J = 8.8 Hz, 1 H), 7.19-
7.17 (m, 3 H), 7.00 (s, 1 H), 6.93 (t, J = 6.8 Hz, 1 H), 6.82 (d, J = 8.4 Hz, 2
H), 4.69 (s, 2 H), 2.79 (s, 3 H), 1.20 (s, 9 H); 13C NMR (100 MHz,
CD3SOCD3) δ 147.7, 140.1, 138.1, 126.1, 125.8, 123.6, 123.3, 117.4,
117.2, 116.4, 114.0, 113.4, 79.6, 48.2, 38.5, 33.9, 31.8; HRMS (EI) calcd
for C21H23N3 [M]þ 317.1892, found 317.1896.
3-((Methyl(phenyl)amino)methyl)indolizine-1-carbonitrile
(3m): 64% yield; white solid; 1H NMR (400 MHz, CDCl3) δ 7.96 (d,
J = 6.8 Hz, 1 H), 7.66 (d, J = 8.8 Hz, 1 H), 7.30 (t, J = 8.0 Hz, 2 H), 7.09 (t,
J = 7.8 Hz, 1 H), 6.95 (s, 1 H), 6.94 (d, J = 8.4 Hz, 2 H), 6.86 (t, J = 7.4 Hz,
1 H), 6.76 (t, J = 6.6 Hz, 1 H), 4.62 (s, 2 H), 2.79 (s, 3 H); 13C NMR (100
MHz, CDCl3) δ 149.9, 138.7, 129.4, 124.4, 122.1, 121.8, 118.7, 117.9,
117.1, 116.9, 114.4, 113.0, 80.9, 48.6, 37.5; HRMS (EI) calcd for
C17H15N3 [M]þ 261.1266, found 261.1271.
2-Methyl-3-((methyl(phenyl)amino)methyl)indolizine-1-
carbonitrile (3n): 64% yield; white solid; 1H NMR (500 MHz,
CD3SOCD3) δ 8.07 (d, J = 7.0 Hz, 1 H), 7.60 (d, J = 9.0 Hz, 1 H), 7.24
(t, J = 8.0 Hz, 2 H), 7.17 (t, J = 7.5 Hz, 1 H), 7.01 (d, J = 8.0 Hz, 2 H),
6.89 (t, J = 6.5 Hz, 1 H), 6.77 (t, J = 7.5 Hz, 1 H), 4.65 (s, 2 H), 2.57 (s, 3
H), 2.34 (s, 3 H); 13C NMR (125 MHz, CD3SOCD3) δ 150.7, 137.1,
129.6, 127.2, 125.4, 123.4, 119.7, 118.5, 116.9, 116.8, 115.0, 113.3, 81.8,
45.7, 36.9, 10.6; HRMS (EI) calcd for C18H17N3 [M]þ 275.1422,
found 275.1428.
Methyl 3-(4-(dimethylamino)benzyl)indolizine-1-carbox-
ylate (4s): 14% yield; white solid; 1H NMR (400 MHz, CDCl3) δ 8.21
(d, J = 9.2 Hz, 1 H), 7.76 (d, J = 6.8 Hz, 1 H), 7.05-7.00 (m, 4 H), 6.69-
6.63 (m, 3 H), 4.09 (s, 2 H), 3.89 (s, 3 H), 2.91 (s, 6 H); 13C NMR (100
MHz, CDCl3) δ 165.5, 149.5, 136.5, 129.0, 124.6, 124.5, 123.2, 121.5,
119.8, 115.5, 113.0, 112.2, 102.4, 50.7, 40.7, 31.4; HRMS (EI) calcd for
C19H20N2O2 [M]þ 308.1525, found 308.1522.
Methyl 3-((methyl(m-tolyl)amino)methyl)indolizine-1-car-
boxylate (3t): 70% yield; white solid; 1H NMR (400 MHz,
CD3SOCD3) δ 8.19 (d, J = 7.2 Hz, 1 H), 8.08 (d, J = 8.8 Hz, 1 H),
7.20 (t, J = 7.8 Hz, 1 H), 7.07 (t, J = 7.6 Hz, 1 H), 6.92 (t, J = 6.4 Hz, 1 H),
6.90 (s, 1 H), 6.71-6.68 (m, 2 H), 6.52 (d, J = 7.2 Hz, 1 H), 4.77 (s, 2 H),
3.75 (s, 3 H), 2.86 (s, 3 H), 2.23 (s, 3 H); 13C NMR (100 MHz,
CD3SOCD3) δ 164.6, 149.9, 138.5, 136.0, 129.3, 125.3, 123.0, 122.7,
119.1, 118.3, 115.2, 114.2, 113.0, 110.8, 102.0, 51.0, 47.9, 38.2, 21.9; HRMS
(EI) calcd for C19H20N2O2 [M]þ 308.1525, found 308.1533.
Methyl 3-(4-(dimethylamino)-2-methylbenzyl)indolizine-
1-carboxylate (4t): 12% yield; white solid; H NMR (400 MHz,
1
CDCl3) δ 8.25 (d, J = 8.8 Hz, 1 H), 7.80 (d, J = 6.8 Hz, 1 H), 7.07 (t, J =
7.8 Hz, 1 H), 6.89 (s, 1 H), 6.81 (d, J = 8.4 Hz, 1 H), 6.73 (t, J = 6.4 Hz, 1
H), 6.65 (s, 1 H), 6.53 (d, J = 8.8 Hz, 1 H), 4.03 (s, 2 H), 3.88 (s, 3 H),
2.94 (s, 6 H), 2.31 (s, 3 H); 13C NMR (125 MHz, CDCl3) δ 165.5,
149.7, 137.1, 136.1, 129.6, 124.3, 123.1, 123.0, 121.4, 119.8, 115.4, 115.0,
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dx.doi.org/10.1021/jo1023975 |J. Org. Chem. 2011, 76, 1759–1766