Borane;tetrahydrofuran → HCID 136348448, compound

Participants

Reaction Steps

To a solution of 4-(4-bromo-2-methylphenyl)-1-ethyl-3-(pyridin-2-yl)-4,5,6,8-tetrahydropyrazolo[3,4-b]azepin-7(1H)-one (0.045 g, 0.11 mmol, Example #AA.1) in THF (2 mL) was added borane tetrahydrofuran complex (1M in THF, 0.74 mL, 0.74 mmol) and the reaction was stirred at rt for about 2 h. The reaction was cooled to 0° C. and carefully quenched with 5M HCl (1 mL) and then stirred about 30 min at rt. The organic solvents were removed in vacuo and the aqueous layer was neutralized with solid Na2CO3 and extracted with EtOAc (2×10 mL). The combined extracts were dried over Na2SO4, filtered and concentrated in vacuo. The crude product was further purified by silica gel column chromatography using a gradient of 65-85% EtOAc in heptane. Product fractions were combined and concentrated in vacuo. The residue was dissolved in ACN (2 mL) and the product was precipitated by addition of water. The product was filtered off and dried in the vacuum oven at about 50° C. to yield 4-(4-bromo-2-methylphenyl)-1-ethyl-3-(pyridin-2-yl)-1,4,5,6,7,8-hexahydropyrazolo[3,4-b]azepine as an off-white solid (0.030 g, 0.073 mmol, 69%); LC-MS (Table 1, Method g) Rt=2.72 min, m/z 411/413 (M+H)+; 1H NMR (400 MHz, DMSO-d6) δ 8.44-8.39 (m, 1H), 7.77-7.72 (m, 1H), 7.68-7.61 (m, 1H), 7.24 (d, J=2.1 Hz, 1H), 7.16-7.09 (m, 2H), 6.92 (d, J=8.3 Hz, 1H), 5.70 (t, J=3.9 Hz, 1H), 5.66-5.58 (m, 1H), 4.13-3.97 (m, 2H), 3.40-3.30 (m, 1H), 2.84-2.74 (m, 1H), 2.45 (s, 3H), 1.92-1.82 (m, 1H), 1.81-1.70 (m, 1H), 1.68-1.57 (m, 1H), 1.57-1.45 (m, 1H), 1.28 (t, J=7.1 Hz, 3H).

Provenance & Evidence