Citation: Xiao-Jian Wang, Yu-Lin Tian, Qing-Yang Zhang, Jian-Guo Qi, Da-Li Yin. An efficient synthesis of substituted 1,4-diazepines by a Pd catalyzed amination and sequential hydrogenation condensation[J]. Chinese Chemical Letters, ;2013, 24(8): 743-746. shu

An efficient synthesis of substituted 1,4-diazepines by a Pd catalyzed amination and sequential hydrogenation condensation

1.
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, China

Corresponding author: Da-Li Yin,
Received Date: 20 March 2013
Available Online: 16 April 2013

An efficient synthesis of substituted 1,4-diazepines is developed. The accessible intermediates have been obtained via Pd-catalyzed amination. The subsequent hydrogenation and intramolecular condensation sequences could be conducted successively in one pot without special operation. The mild and general strategy enables the synthesis of various substituted 1,4-diazepines in high yields.
- 1,4-Diazepines,
- Pd-catalyzed amination,
- Hydrogenation,
- Intramolecular condensation
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  [15] Compound 5a: ¹H NMR (300 MHz, CD3Cl): δ 7.710 (d, 2H, J = 5.4 Hz), 7.404 (m, 3H), 7.323 (m, 2H), 7.014 (m, 3H), 6.918 (m, 1H), 6.779 (m, 1H), 6.704 (m, 1H), 4.975 (s, 1H). ¹³C NMR (100 MHz, CDC_l3): δ 169.49, 154.45, 142.60, 141.32, 140.85, 132.19, 131.94, 129.93, 128.67, 127.96, 127.56, 126.81, 124.17, 122.42, 119.70. HRMS (m/z) (M+H): Calcd. for C₁₉H₁₄N₂: 271.123, found: 271.1233. Mp 129-131℃. IR (KBr): 3350, 1609, 1571, 1445, 1283, 960. Compound 5b: ¹H NMR (300 MHz, CD3Cl): δ 7.69 (d, 1H, J = 6.6 Hz), 7.44 (m, 3H), 7.38 (td, 1H, J = 7.8 Hz, J = 1.5 Hz), 7.01 (m, 2H), 6.93 (m, 2H), 6.77 (d, 1H, J = 4.5 Hz), 6.72 (dd, 1H, J = 7.8 Hz, J = 2.7 Hz), 6.63 (m, 1H), 4.97 (s, 1H). ¹³C NMR (100 MHz, CDC_l3): δ 170.58, 160.97, 158.58, 154.50, 142.05 (J = 9 Hz), 140.90, 138.64, 132.15 (J = 6 Hz), 130.26, 129.64, 128.01, 127.45, 122.60, 120.08 (J = 9 Hz), 119.69, 114.58 (J = 23 Hz), 112.88 (J = 23 Hz). HRMS (m/z) (M+H): Calcd. for C19H13FN2: 289.1136, found: 289.1142. Mp 103-105℃. IR (KBr): 3352, 1613, 1466, 1216, 1107, 866. Compound 5c: ¹H NMR (300 MHz, CD3Cl): δ 7.70 (d, 2H, J = 7.8 Hz), 7.43 (m, 3H), 7.37 (m, 1H), 6.99 (d, 1H, J = 7.5 Hz), 6.89 (m, 2H), 6.74 (d, 1H, J = 7.5 Hz), 6.60 (s, 2H), 3.77 (s, 3H). ¹³C NMR (100 MHz, CDC_l3): δ 170.00, 156.61, 155.03, 141.67, 141.29, 135.77, 132.15, 131.94, 129.97, 129.58, 127.94, 127.44, 122.28, 120.24, 119.51, 113.13, 112.55, 55.59. HRMS (m/z) (M+H): Calcd. for C₂0H₁₆N₂O: 301.1335, found: 301.1339. Mp 149-152℃. IR (KBr): 3349, 2400, 1666, 1501, 1328, 1243, 1117, 960. Compound 5d: ¹H NMR (300 MHz, CD3Cl): δ 7.70 (d, 2H, J = 6.9 Hz), 7.56 (s, 1H), 7.41 (m, 3H), 7.27 (m, 2H), 6.97 (m, 2H), 6.74 (t, 2H, J = 7.5 Hz), 5.12 (s, 1H). ¹³C NMR (100 MHz, CDC_l3): δ 170.85, 153.40, 145.85, 140.77, 140.72, 132.38, 132.36, 130.41, 129.62, 128.07, 127.50, 126.01, 125.98, 123.51, 123.47, 122.93, 119.99, 119.85. HRMS (m/z) (M+H): Calcd. for C₂₀H₁₃F₃N₂: 339.1104, found: 339.1105. Mp 129-131℃. IR (KBr): 3267, 2400, 1607, 1445, 1325, 1123, 1074, 960, 751. Compound 5e: ¹H NMR (300 MHz, CD3Cl): δ 7.95 (d, 1H, J = 4.8 Hz), 7.68 (d, 2H, J = 7.5 Hz), 7.56 (d, 1H, J = 7.8 Hz), 7.38 (m, 3H), 7.29 (t, 1H, J = 7.5 Hz), 7.01 (m, 2H), 6.92 (m, 1H), 6.83 (d, 1H, J = 5.1 Hz Hz), 6.19 (s, 1H). ¹³C NMR (100 MHz, CDC_l3): δ 171.06, 153.39, 152.01, 145.05, 140.80, 136.52, 135.24, 132.51, 132.30, 130.27, 129.64, 128.01, 127.13, 122.32, 120.40, 119.98. HRMS (m/z) (M+H): Calcd. for C18H13N3: 272.1182, found: 272.1187. Mp 183-186℃. IR (KBr): 3277, 2380, 1703, 1454, 1227, 1021, 960. Compound 5f: ¹H NMR (300 MHz, CD3Cl): δ 7.67 (d, 2H, J = 6.9 Hz), 7.42 (m, 3H), 7.30 (m, 2H), 6.95 (m, 3H), 6.76 (d, 1H, J = 8.1 Hz), 6.61 (d, 1H, J = 8.1 Hz). ¹³C NMR (100 MHz, CDC_l3): δ 170.78, 154.18, 119.84, 141.75, 141.40, 140.71, 132.30, 130.39, 129.67, 129.09, 128.13, 128.04, 127.34, 126.40, 122.71, 120.58. HRMS (m/z) (M+H): Calcd. for C19H14ClN2: 305.0840, found: 305.0845. Mp 191-193℃. IR (KBr): 3274, 2336, 1601, 1423, 1255, 1064, 960. Compound 5g: ¹H NMR (400 MHz, CD3Cl): δ 7.98 (s, 1H), 7,60 (m, 3H), 7.42-7.52 (m, 3H), 7,35 (t, 1H, J = 5.4 Hz), 7.03 (m, 1H), 7.01 (m, 1H), 6.79 (d, 1H, J = 7.6 Hz), 6.73 (d, 1H, J = 7.6 Hz), 5.21 (s, 1H). ¹³C NMR (100 MHz, CDC_l3): δ 166.552, 153.289, 147.334, 140.777, 132.660, 132.477, 132.344, 130.495, 130.320, 130.045, 129.641, 128.398, 128.036, 127.399, 126.095, 122.809, 120.019, 119.592, 51.968. HRMS (m/z) (M+H): Calcd. for C₂₁H₁₇O₂N₂, 329.1284, found 329.1286. Mp 159-162℃. IR (KBr): 3285, 1238, 1078, 1054, 975, 730. Compound 5h: ¹H NMR (400 MHz, CD3Cl): δ 7.60 (d, 2H, J = 8 Hz), 7.29 (m, 2H), 7.19 (m, 2H), 7.02 (m, 3H), 6.91 (t, 1H, J = 7.2 Hz), 6.77 (d, 1H, J = 8 Hz), 6.69 (d, 1H, J = 6.8 Hz), 4.97 (s, 1H). ¹³C NMR (100 MHz, CDC_l3): δ 169.36, 154.39, 142.62, 140.95, 140.12, 138.49, 132.18, 131.82, 129.54, 128.64, 127.59, 126.57, 124.10, 122.32, 119.67, 119.66, 21.38. HRMS (m/z) (M+H): Calcd. for C₂0H₁₆N₂: X.-J. Wang et al. / Chinese Chemical Letters 24 (2013) 743-746 745 285.1386, found: 285.1386. Mp 168-170℃. IR (KBr): 3347, 1577, 1466, 1238, 876. Compound 5i: ¹H NMR (400 MHz, CD3Cl): δ 7.59 (d, 2H, J = 7.6 Hz), 7.29 (m, 1H), 7.20 (m, 2H), 7.03 (m, 2H), 6.94 (m, 1H), 6.78 (d, 1H, J = 8 Hz), 6.71 (m, 1H), 6.62 (m, 1H), 4.92 (s, 1H), 2.40 (s, 3H). ¹³C NMR (100 MHz, CDC_l3): δ 170.43, 160.92, 158.53, 154.43, 142.14, 140.53, 138.66, 138.06, 132.01 (J = 17 Hz), 129.62, 128.69, 127.46, 122.49, 120.11, 119.65, 114.40 (J = 24 Hz), 112.61 (J = 23 Hz), 21.36. HRMS (m/z) (M+H): Calcd. for C20H15FN2: 303.1292, found: 303.1296. Mp 145-148℃. IR (KBr): 3345, 1620, 1487, 1220, 1113, 960. Compound 5j: ¹H NMR (400 MHz, CD3Cl): δ 7.60 (d, 2H, J = 7.6 Hz), 7.31 (m, 1H), 7.19 (d, 2H, J = 7.6 Hz), 7.02 (m, 1H), 6.91 (t, 1H, J = 7.6 Hz), 6.88 (s, 1H), 6.77 (d, 1H, J = 8 Hz), 6.65 (m, 2H). ¹³C NMR (100 MHz, CDC_l3): δ 169.87, 156.60, 154.98, 141.80, 140.20, 138.47, 135.80, 132.19, 131.83, 129.59, 128.65, 127.51, 122.23, 120.18, 119.48, 112.93, 112.44, 55.59, 21.38. HRMS (m/z) (M+H): Calcd. for C21H18N2O: 315.1492, found 315.1495. Mp 178-180℃. IR (KBr): 3300, 1567, 1433, 1203, 1103, 982. Compound 5k: ¹H NMR (400 MHz, CD3Cl): δ 7.60 (d, 2H, J = 8 Hz), 7.55 (m, 1H), 7.31 (m, 1H), 7.21 (m, 5H), 7.05 (m, 1H), 6.95 (m, 1H), 6.75 (m, 2H), 5.11 (s, 1H), 2.41 (s, 3H). ¹³C NMR (100 MHz, CDC_l3): δ 170.67, 153.36, 145.84, 140.91, 140.75, 137.91, 132.41, 132.24, 129.64, 128.87, 127.58, 125.90, 125.87, 123.27, 123.24, 122.87, 119.94, 119.78, 21.42. HRMS (m/z) (M+H): Calcd. for C21H15F3N2: 353.1260, found: 353.1264. Mp 180-183℃. IR (KBr): 3309, 2740, 1637, 1325, 1076, 960, 751. Compound 5l: ¹H NMR (400 MHz, CD3Cl): δ 7.93 (d, 1H, J = 4 Hz), 7.55 (m, 3H), 7.31 (t, 1H, J = 7.6 Hz), 7.21 (d, 2H, J = 7.6 Hz), 6.98 (m, 2H), 6.91 (m, 1H), 6.84 (m, 1H), 5.91 (s, 1H), 2.41 (s, 3H). ¹³C NMR (100 MHz, CDC_l3): δ 170.93, 153.31, 151.96, 144.88, 140.62, 138.00, 136.36, 135.32, 132.42, 132.35, 129.68, 128.74, 127.17, 122.31, 120.37, 120.02, 21.42. HRMS (m/z) (M+H): Calcd. for C19H15N3: 286.1339, found: 286.1347. Mp 175-177℃. IR (KBr): 3223, 2246, 1667, 1411, 1227, 1021, 960.
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沈阳化工大学材料科学与工程学院沈阳 110142