Water → HCID 136348420, compound

Participants

Reaction Conditions

Reaction Steps

To a mixture of 1-methyl-4-(4-piperidyl)-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepine dihydrochloride (0.10 g, 0.25 mmol) and N,N-diisopropylethylamine (0.14 mL, 0.8 mmol) in DCM (20 mL) was added dropwise a solution of acetyl chloride (0.018 mL, 0.25 mmol) in DCM (2 mL), at about −10° C. The resulting mixture was stirred at about −10° C. for about 2 h and about 1 h at rt, then water (10 mL) and DCM (20 mL) were added. The layers were separated and the organic layer was washed with water (10 mL) and brine (10 mL), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (SiO2, DCM/methanol 95:5) to give 1-[4-[1-methyl-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepin-4-yl]-1-piperidyl]ethanone (0.090 g, 97%) as a white solid: LC-MS (Table 1, Method a) Rt=1.60 min; m/z 372 (M+H)+; 1H-NMR (CDCl3, Bruker 400 MHz) (The spectrum is described as a 1:1 mixture of two compounds (‘rotamers’), each contributing 25 protons) δ 1.11 (1H, td, J=12.4, 4.3 Hz) 1.17-1.37 (4H, m) 1.38-1.50 (2H, m) 2.01 (3H, s) 2.07 (3H, s) 2.08-2.28 (4H, m) 2.39 (1H, td, J=12.7, 2.9 Hz) 2.65-2.74 (2H, m) 2.86 (1H, td, J=12.8, 2.9 Hz) 2.96-3.13 (5H, m) 3.39-3.54 (4H, m) 3.65 (1H, br. d, J=13.6 Hz) 3.77 (3H, s) 3.78 (3H, s) 3.84 (1H, br. d, J=13.6 Hz) 4.40 (1H, br. d, J=13.5 Hz) 4.63 (1H, br. d, J=13.7 Hz) 5.04 (1H, d, J=9.5 Hz) 5.06 (1H, d, J=9.9 Hz) 7.11-7.17 (2H, m) 7.63-7.69 (2H, m) 7.84-7.92 (2H, m) 8.50-8.56 (2H, m).

Provenance & Evidence