73% |
With sodium tris(acetoxy)borohydride; In 1,2-dichloro-ethane; at 20.0℃; |
General procedure: 3.2.28 1-(3-Phenylpropyl)-4-(pyridin-3-yl)-1,4-diazepane (32) Compound 32 was prepared as described for 28 from a mixture of <strong>[223796-20-1]1-(pyridin-3-yl)-1,4-diazepane</strong> (100 mg, 0.56 mmol), 3-phenylpropanal (82 muL, 0.56 mmol, 90%), and NaBH(OAc)3 (178 mg, 0.84 mmol) yielding the product as an orange oil (121 mg, 73%). 1H NMR (CDCl3, 400 MHz) delta 8.12 (d, 1H, J = 2.9 Hz), 7.92 (dd, 1H, J = 4.6, 1.3 Hz), 7.29-7.25 (m, 3H), 7.20-7.14 (m, 3H), 7.09 (ddd, 1H, J = 8.5, 4.6, 0.7 Hz), 6.93 (ddd, 1H, J = 8.6, 3.1, 1.3 Hz), 3.56 (t, 2H, J = 4.9 Hz), 3.50 (t, 2H, J = 6.3 Hz), 2.80-2.77 (m, 2H), 2.66-2.59 (m, 4H), 2.52 (t, 2H, J = 7.4 Hz), 2.01-1.96 (m, 2H), 1.81 (p, 2H, J = 7.5 Hz). 13C NMR (CDCl3, 101 MHz) delta 144.99, 142.16, 137.31, 134.48, 128.53 (2C), 128.47 (2C), 125.94, 123.73, 117.92, 57.23, 55.07, 54.54, 48.64, 47.86, 33.63, 29.12, 27.45. 1-(3-Phenylpropyl)-4-(pyridin-3-yl)-1,4-diazepane oxalate. The free amine of 32 (121 mg, 0.41 mmol) was converted into the oxalate salt as described under the general procedure affording a yellow solid (55 mg, 35%). Mp: 59.3-60.3 C. 1H NMR (D2O, 400 MHz) delta 8.13 (d, 1H, J = 2.9 Hz), 8.07 (d, 1H, J = 5.2 Hz), 7.88 (ddd, 1H, J = 9.1, 2.9, 1.0 Hz), 7.82 (dd, 1H, J = 9.0, 5.3 Hz), 7.40-7.37 (m, 2H), 7.32-7.28 (m, 3H), 3.89 (t, 2H, J = 4.7 Hz), 3.68-3.56 (m, 4H), 3.50-3.25 (m, 2H), 3.22-3.18 (m, 2H), 2.75 (t, 2H, J = 7.3 Hz), 2.33-2.27 (m, 2H), 2.16-2.08 (m, 2H). 13C NMR (D2O, 101 MHz) delta 168.27 (2C), 146.92, 140.37, 128.79 (2C), 128.58 (2C), 128.50, 127.55, 127.16, 126.57, 124.21, 56.08, 54.04, 53.59, 46.51, 43.18, 31.71, 25.31, 23.47.; 3.2.24. 1-(6-Bromopyridin-3-yl)-4-(3-phenylpropyl)-1,4-diazepane(28); A solution of 58 (598 mg, 1.68 mmol) and TFA (2.58 mL,33.7 mmol) in DCM (20 mL) was stirred at rt for 16 h. The reaction mixture was evaporated in vacuo. The residue was added aq NaOHsolution (4 M, 20 mL) and extracted with DCM (3 100 mL). The combined organic phases were dried (MgSO4), filtered, and evaporatedin vacuo giving 1-(6-bromopyridin-3-yl)-1,4-diazepane as ayellow oil (274 mg, 64%) that crystallizes over time. To a solution 1-(6-bromopyridin-3-yl)-1,4-diazepane (274 mg, 1.07 mmol) and phenylpropanal (157 mL,1.07 mmol, 90%) in dry DCE (10 mL) was added freshly grinded NaBH(OAc)3 (340 mg, 1.61 mmol). The reaction mixture was stirred overnight at rt. Sat. aq NaHCO3 solution (10 mL) was added to thereaction mixture that was extracted with DCM (2 5 mL). The combined organic phases were washed with sat. aq NaHCO3 solution (10 mL), dried (MgSO4), filtered, and evaporated in vacuo. Purification by DCVC (DCM:MeOH:NH3/100:0:0 to 97.5:2.25:0.25) afforded the product as a yellow oil (362 mg, 90%). |