The Journal of Organic Chemistry
Article
mg, 0.201 mmol, 80%) from 2c according to general procedure C: 1H
NMR δ 1.48 (9H, s), 2.77 (4H, br m), 3.48 (4H, br m), 3.81 (3H, s),
6.89 (2H, t, J 6.9 Hz), 7.32 (2H, dd, J 14.6, 8.2 Hz), 10.15 (1H, br);
13C NMR δ 25.2, 25.8, 28.6, 28.8 (br), 29.4 (br), 47.0, 47.7, 48.9, 49.5,
55.4, 79.7, 114.1, 115.0, 115.2, 124.2 (br), 124.5 (br), 129.5, 129.6,
145.4 (br), 147.6 (br), 154.9, 159.5; FTIR (υmax cm−1) 3181, 2934,
1680, 1616, 1513, 1458, 1414, 1366, 1298, 1246, 1164, 1106, 1035,
985, 922, 908, 834, 773, 728; Rf 0.27 (33% acetone/CH2Cl2); HRMS
(ESI+) calculated for C19H26N3O3 [M + H]+ 344.1974, found
344.1993.
HRMS (ESI+) calculated for C16H22N3O2S [M + H]+ 320.1427, found
320.1421.
tert-Butyl 3-Benzyl-4,5,7,8-tetrahydropyrazolo[3,4-d]azepine-
6(2H)-carboxylate (3j). Isolated as a white gum (56.5 mg, 0.173
1
mmol, 69%) from 2j, according to general procedure C: H NMR δ
1.47 (9H, app d, J 6.4 Hz), 2.56 (2H, br), 2.85 (2H, br), 3.45−3.55
(4H, br m), 3.90 (1H, s), 3.92 (1H, s), 7.14−7.27 (5H, m), 7.95 (1H,
br); 13C NMR δ 24.7, 25.2, 28.7, 28.8 (br), 29.6 (br), 31.6 (br), 31.8
(br), 47.2, 47.8, 48.8, 49.3, 79.8, 115.6, 115.8, 126.55, 126.62, 128.5,
128.7, 128.8, 138.5 (br), 138.7 (br), 143.6 (br), 146.9 (br), 154.9;
FTIR (υmax cm−1) 3182, 2928, 1679, 1458, 1415, 1366, 1248, 1163,
1112, 1054, 923, 909, 858, 726, 696; Rf 0.55 (33% acetone/CH2Cl2);
HRMS (ESI+) calculated for C19H26N3O2 [M + H]+ 328.2025, found
328.2017.
tert-Butyl 3-(4-Cyanophenyl)-4,5,7,8-tetrahydropyrazolo[3,4-d]-
azepine-6(2H)-carboxylate (3d). Isolated as a white gum (40.4 mg,
1
0.119 mmol, 48%) from 2d, according to general procedure C: H
NMR δ 1.49 (9H, s), 2.83 (4H, br), 3.55 (4H, br), 7.57 (1H, d, J 7.9
Hz), 7.60 (1H, d, J 8.0 Hz), 7.68 (2H, d, J 7.8 Hz), 10.96 (1H, br); 13C
NMR δ 25.3, 25.9, 28.1 (br), 28.65, 28.72 (br), 46.7, 47.3, 48.6, 49.2,
80.2, 111.4, 111.5, 116.1, 116.5, 118.8 (br), 128.7, 128.8, 132.4, 132.5,
137.6 (br), 145.0 (br), 154.8, 154.9; FTIR (υmax cm−1) 3218, 2975,
2228, 1666, 1610, 1461, 1414, 1366, 1340, 1243, 1161, 1106, 985, 923,
844, 773, 728; Rf 0.54 (33% acetone/CH2Cl2); HRMS (ESI+)
calculated for C19H22N4O2Na [M + Na]+ 361.1635, found 361.1626.
tert-Butyl 3-(3-Fluorophenyl)-4,5,7,8-tetrahydropyrazolo[3,4-d]-
azepine-6(2H)-carboxylate (3e). Isolated as a white gum (60.1 mg,
tert-Butyl 3-(Cyclohex-1-en-1-yl)-4,5,7,8-tetrahydropyrazolo[3,4-
d]azepine-6(2H)-carboxylate (3k). Isolated as a white gum (53.5 mg,
1
0.169 mmol, 68%) from 2k, according to general procedure C: H
NMR δ 1.48 (9H, s), 1.64 (2H, br), 1.72 (2H, br), 2.17 (2H, br), 2.29
(2H, br), 2.70 (2H, br), 2.89 (2H, br), 3.52 (4H, br), 5.84 (1H, m),
8.65 (1H, br); 13C NMR δ 22.0, 22.8, 25.5, 25.6, 26.1, 28.06, 28.10,
28.7, 29.3 (br), 30.0 (br), 47.1, 47.7, 48.7, 49.4, 79.7, 114.6, 114.8,
128.2 (br), 128.6 (br), 128.7, 128.9, 145.3 (br), 148.8 (br), 155.0;
FTIR (υmax cm−1) 3181, 2932, 1674, 1459, 1414, 1366, 1247, 1163,
1113, 914, 728; Rf 0.57 (33% acetone/CH2Cl2); HRMS (ESI+)
calculated for C18H28N3O2 [M + H]+ 318.2182, found 318.2174.
tert-Butyl 3-Cyclopropyl-4,5,7,8-tetrahydropyrazolo[3,4-d]-
azepine-6(2H)-carboxylate (3l). Isolated as a white gum (45.8 mg,
1
0.181 mmol, 73%) from 2e, according to general procedure C: H
NMR δ 1.49 (9H, s), 2.73 (4H, br), 3.49 (4H, br), 7.02 (1H, t, J 7.9
Hz), 7.15 (1H, m), 7.21 (1H, dd, J 17.6, 7.2 Hz), 7.33 (1H, br m),
12.14 (1H, br); 13C NMR δ 25.1, 25.8, 28.5 (br), 28.6, 29.4 (br), 46.8,
47.5, 48.8, 49.4, 79.9, 114.8 (br d, J 8.9 Hz), 114.9 (br d, J 9.3 Hz),
115.3 (d, J 21.8 Hz), 115.7 (d, J 29.8 Hz), 124.1, 130.2 (d, J 7.5 Hz),
134.7 (br), 146.5 (br), 154.88, 154.94, 162.9 (d, J 244.9 Hz); FTIR
(υmax cm−1) 3183, 2934, 1668, 1589, 1457, 1414, 1366, 1241, 1162,
1115, 1103, 1005, 924, 907, 861, 788, 728; Rf 0.50 (33% acetone/
CH2Cl2); HRMS (ESI+) calculated for C18H23N3O2F [M + H]+
332.1769, found 332.1767.
1
0.165 mmol, 66%) from 2l, according to general procedure C: H
NMR δ 0.70 (2H, m), 0.86 (2H, m), 1.48 (9H, s), 1.71 (1H, m), 2.71
(2H, br), 2.84 (2H, br), 3.53 (4H, br), 8.67 (1H, br); 13C NMR δ 6.06
(br), 6.14, 6.2, 24.5, 25.1, 28.7, 28.8 (br), 29.5 (br), 47.3, 47.8, 48.9,
49.5, 79.7, 116.2, 116.5, 142.6 (br), 146.8 (br), 154.96, 154.99; FTIR
(υmax cm−1) 3129, 2932, 1675, 1460, 1413, 1366, 1248, 1164, 1112,
1037, 1019, 924, 908, 859, 773, 729; Rf 0.44 (33% acetone/CH2Cl2);
HRMS (ESI+) calculated for C15H24N3O2 [M + H]+ 278.1869, found
278.1862.
tert-Butyl 3-(2-(Trifluoromethyl)phenyl)-4,5,7,8-tetrahydro-
pyrazolo[3,4-d]azepine-6(2H)-carboxylate (3f). Isolated as a white
gum (39.9 mg, 0.105 mmol, 42%) from 2f, according to general
tert-Butyl 3-Cyclopentyl-4,5,7,8-tetrahydropyrazolo[3,4-d]-
azepine-6(2H)-carboxylate (3m). Isolated as a white gum (57.9 mg,
1
1
procedure C: H NMR δ 1.47 (9H, app d, J 23.6 Hz), 2.44 (2H, br),
0.190 mmol, 75%) from 2m, according to general procedure C: H
2.75 (2H, br), 3.47 (4H, br), 7.34 (1H, t, J 7.7 Hz), 7.53 (1H, t, J 7.6
Hz), 7.58 (1H, t, J 7.4 Hz), 7.76 (1H, d, J 7.8 Hz), 10.76 (1H, br); 13C
NMR δ 24.9, 25.6, 28.63, 28.67, 28.72 (br), 47.1, 47.8, 48.8, 49.4, 79.8,
117.5 (br), 117.7 (br), 123.9 (q, J 272.3 Hz), 126.4 (q, J 4.5 Hz),
128.9, 129.0 (q, J 6.0 Hz), 131.2 (q, J 32.9 Hz), 131.6, 133.0, 143.6
(br), 146.6 (br), 154.9, 155.0; FTIR (υmax cm−1) 3195, 2931, 1683,
1460, 1413, 1367, 1314, 1247, 1162, 1127, 1108, 1059, 1034, 991, 925,
859, 769, 730; Rf 0.59 (33% acetone/CH2Cl2); HRMS (ESI+)
calculated for C19H23N3O2F3 [M + H]+ 382.1737, found 382.1740.
tert-Butyl 3-(Naphthalen-1-yl)-4,5,7,8-tetrahydropyrazolo[3,4-d]-
azepine-6(2H)-carboxylate (3g). Isolated as a white gum (49.8 mg,
NMR δ 1.47 (9H, s), 1.64 (4H, br), 1.76 (2H, br), 1.99 (2H, br), 2.61
(2H, m), 2.86 (2H, m), 3.00 (1H, quint, J 8.1 Hz), 3.53 (4H, br m),
9.14 (1H, br); 13C NMR δ 24.7, 25.3, 25.4, 28.6, 29.0 (br), 29.8 (br),
32.5, 36.5 (br), 36.7 (br), 47.2, 47.8, 48.9, 49.4, 79.7, 114.6 (br), 114.8
(br), 147.6 (br), 148.3 (br), 155.0; FTIR (υmax cm−1) 3182, 2948,
1675, 1459, 1413, 1366, 1247, 1164, 1111, 925, 908, 859, 773, 729; Rf
0.55 (33% acetone/CH2Cl2); HRMS (ESI+) calculated for
C17H28N3O2 [M + H]+ 306.2176, found 306.2174.
tert-Butyl 3-Butyl-4,5,7,8-tetrahydropyrazolo[3,4-d]azepine-
6(2H)-carboxylate (3n). Isolated as a white gum (54.6 mg, 0.186
1
mmol, 74%) from 2n, according to general procedure C: H NMR δ
1
0.137 mmol, 55%) from 2g, according to general procedure C: H
0.89 (3H, app q, J 7.4 Hz), 1.33 (2H, quint, J 7.9 Hz), 1.48 (9H, s),
1.53 (2H, q, J 7.6 Hz), 2.53 (2H, t, J 7.8 Hz), 2.58 (2H, td, J 21.4, 4.5
Hz), 2.87 (2H, td, J 19.3, 4.5 Hz), 3.52 (4H, app tt, J 19.0, 4.7 Hz),
9.35 (1H, br); 13C NMR δ 14.0, 22.5, 22.6, 24.6, 24.9, 25.1, 25.2, 28.7,
29.1 (br), 29.8 (br), 31.8, 47.3, 47.9, 49.0, 49.5, 79.7, 114.9 (br), 115.1
(br), 145.0 (br), 147.8 (br), 155.0; FTIR (υmax cm−1) 3196, 2932,
1677, 1459, 1414, 1366, 1247, 1165, 1112, 963, 923, 909, 859, 773,
728; Rf 0.38 (33% acetone/CH2Cl2); HRMS (ESI+) calculated for
C16H28N3O2 [M + H]+ 294.2176, found 294.2179.
3-Phenyl-4,5,7,8-tetrahydro-2H-oxepino[4,5-c]pyrazole (3o). Iso-
lated as a white amorphous solid (45.8 mg, 0.214 mmol, 86%) from
2o, according to general procedure C: 1H NMR δ 2.77 (2H, dd, J 5.0,
4.9 Hz), 2.84 (2H, dd, J 5.0, 4.9 Hz), 3.75 (2H, dd, J 5.1, 5.0 Hz), 3.79
(2H, dd, J 5.0, 4.9 Hz), 7.34 (1H, t, J 7.3 Hz), 7.39 (2H, t, J 7.1 Hz),
7.44 (2H, d, J 7.0 Hz), 10.52 (1H, br); 13C NMR δ 27.8, 31.3 (br),
70.9, 73.0, 116.1 (br), 128.1, 128.3, 128.8, 131.9 (br), 145.2 (br), 148.4
(br); FTIR (υmax cm−1) 3126, 2855, 1499, 1446, 1383, 1333, 1167,
1101, 1041, 1009, 933, 804, 774, 750, 701; Rf 0.42 (33% acetone/
CH2Cl2); HRMS (ESI+) calculated for C13H15N2O [M + H]+
215.1184, found 215.1194.
NMR δ 1.44 (9H, app d, J 33.7 Hz), 2.44 (4H, br m), 3.36 (4H, br m),
7.42−7.49 (4H, m), 7.77 (1H, dd, J 12.7, 8.6 Hz), 7.87−7.89 (2H, m),
11.54 (1H, br); 13C NMR δ 25.2, 25.8, 28.3 (br), 28.6, 28.7, 47.0, 47.6,
48.8, 49.4, 79.6, 117.4 (br), 125.3, 125.90, 125.92, 126.2, 126.6, 126.7,
128.3, 128.4, 129.0 (br), 129.5 (br), 132.4 (br), 133.7, 143.4 (br),
147.2 (br), 154.8, 154.9; FTIR (υmax cm−1) 3182, 2930, 1682, 1413,
1366, 1295, 1243, 1162, 1111, 1046, 961, 923, 908, 803, 777, 727; Rf
0.55 (33% acetone/CH2Cl2); HRMS (ESI+) calculated for
C22H26N3O2 [M + H]+ 364.2020, found 364.2011.
tert-Butyl 3-(Thiophen-2-yl)-4,5,7,8-tetrahydropyrazolo[3,4-d]-
azepine-6(2H)-carboxylate (3i). Isolated as a pale yellow amorphous
solid (26.3 mg, 0.0823 mmol, 33%) from 2i, according to general
1
procedure C: H NMR δ 1.49 (9H, s), 2.85 (4H, br), 3.54 (4H, br),
7.08 (1H, t, J 4.5 Hz), 7.16 (1H, app dd, J 14.3, 2.6 Hz), 7.31 (1H, d, J
5.0 Hz); 13C NMR δ 25.2, 25.8, 28.2 (br), 28.7, 28.9 (br), 46.9, 47.5,
48.6, 49.2, 79.9, 115.6 (br), 116.0 (br), 125.5, 125.6, 125.65, 125.74,
127.6, 127.7, 134.4 (br), 141.2 (br), 145.4 (br), 154.9, 155.0; FTIR
(υmax cm−1) 3455, 2968, 1654, 1467, 1419, 1366, 1246, 1168, 1119,
1023, 941, 924, 846, 775, 727, 694; Rf 0.56 (33% acetone/CH2Cl2);
8808
dx.doi.org/10.1021/jo501624t | J. Org. Chem. 2014, 79, 8800−8811