p-Toluenesulfonic acid → HCID 136348447, compound

Participants

Reaction Steps

A solution of methyl 4-(4-bromo-2-methylphenyl)-4-(5-((tert-butoxycarbonyl)amino)-1-ethyl-3-(pyridin-2-yl)-1H-pyrazol-4-yl)butanoate (0.072 g, 0.129 mmol, Prepared using W from 4-bromobenzaldehyde, X from 1-ethyl-3-(pyridin-2-yl)-1H-pyrazol-5-amine, Y then Z) in DCM (3 mL) was treated with TFA (3 mL) and the reaction was stirred for about 20 min at rt. Solvents were removed in vacuo and the residue was taken up in toluene (5 mL) containing p-TSA (0.049 g, 0.26 mmol) and the reaction was heated at about 100° C. for about 3 h. The reaction was cooled to rt, diluted with EtOAc (5 mL) to solubilize the product and washed with sat. aq. NaHCO3 (5 mL), then water (5 mL). The organic layer was dried over Na2SO4, filtered and concentrated in vacuo. Crude product was further purified on silica gel (4 g) using a gradient of 60-90% EtOAc in heptane. Product fractions were combined and concentrated to solids and dried in the vacuum oven overnight to yield 4-(4-bromo-2-methylphenyl)-1-ethyl-3-(pyridin-2-yl)-4,5,6,8-tetrahydropyrazolo[3,4-b]azepin-7(1H)-one as an off-white solid (0.037 g, 0.087 mmol, 67%); LC-MS (Table 1, Method g) Rt=2.31 min, m/z 425/427 (M+H)+; 1H NMR (400 MHz, CDCl3) δ 8.37-8.30 (m, 1H), 7.84 (br. s, 1H), 7.63 (d, J=8.1 Hz, 1H), 7.58-7.48 (m, 1H), 7.14 (s, 1H), 7.06-6.94 (m, 2H), 6.61 (d, J=8.3 Hz, 1H), 5.30-5.20 (m, 1H), 4.20 (q, J=7.3 Hz, 2H), 2.74-2.66 (m, 2H), 2.47 (s, 3H), 2.41-2.30 (m, 1H), 1.94-1.83 (m, 1H), 1.50 (t, J=7.2 Hz, 3H).

Provenance & Evidence