Thioglycolic Acid → HCID 136348413, compound

Participants

Reaction Conditions

Reaction Steps

To 4-(4-chloro-2-methyl-phenyl)-3-[2-[(4-methoxyphenyl)methyl]pyrazol-3-yl]-1-methyl-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepine (0.32 g, 0.67 mmol, prepared using A with ethyl 1-(4-methoxybenzyl)-1H-pyrazole-5-carboxylate (WO2011079076), B with methylhydrazine, C with thioglycolic acid and 4-chloro-2-methylbenzaldehyde (Fluorochem) and D) was added trifluoroacetic acid (5 mL). The resulting mixture was heated, in a sealed microwave vessel, for about 10 min, at about 140° C., in a microwave. After cooling to rt the mixture was made basic (pH ˜8) with 2 M aqueous NaOH and extracted with ethyl acetate. The organic layer was dried (MgSO4), filtered and concentrated in vacuo. The resulting residue was purified by column chromatography (SiO2, ethyl acetate) to give 4-(4-chloro-2-methyl-phenyl)-1-methyl-3-(1H-pyrazol-3 or 5-yl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepine (0.151 g, 0.42 mmol, 63%) as an off white solid: LC-MS (Table 1, Method e) Rt=2.83 min, m/z 360 (M+H)+; 1H-NMR (CDCl3, Bruker 400 MHz) 2.54 (3H, s) 2.64-2.72 (1H, m) 2.77-2.86 (1H, m) 3.21-3.31 (1H, m) 3.54-3.63 (1H, m) 3.77-3.83 (1H, br s) 3.81 (3H, s) 5.69 (1H, br. S.) 6.18 (1H, br s) 7.04 (1H, dd, J=8.5, 2.0 Hz) 7.08 (1H, d, J=8.5 Hz) 7.20 (1H, br s) 7.47 (1H, d, J=2.0 Hz) 10.1 (1H, br s).

Provenance & Evidence