Carbon Dioxide → HCID 136348437, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 4-(4-bromo-2-methylphenyl)-1,3-dimethyl-4,5,6,8-tetrahydropyrazolo[3,4-b]azepin-7(1H)-one (0.143 g, 0.41 mmol, prepared using W from 4-bromo-2-methylbenzaldehyde (Ark Pharm, Inc), X from 1,3-dimethyl-1H-pyrazol-5-amine, Y, Z, then AA) in dry THF (20 mL) was cooled to about −78° C. under nitrogen. A solution of n-BuLi (0.66 mL, 1.64 mmol) (2.5M in THF) was added dropwise maintaining the reaction temperature below about −70° C. The mixture was stirred for about an additional 10 min at about −78° C. and then a stream of CO2 generated from dry ice was bubbled through the solution for about 15 min. Cooling was removed and the reaction was allowed to warm to rt. The reaction was concentrated to solids and then acidified with 2N HCl (2 mL) and extracted with EtOAc (2×10 mL). The EtOAc extracts were dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified on silica gel using a gradient of 0-10% MeOH in DCM. Product fractions were combined and concentrated in vacuo and dried on vacuum pump to yield 4-(1,3-dimethyl-1,4,5,6,7,8-hexahydropyrazolo[3,4-b]azepin-4-yl)-3-methylbenzoic acid as an off white solid (0.055 g, 0.18 mmol, 53%); LC-MS (Table 1, Method g) Rt=1.37 min, m/z 312 (M−H)−. The carboxylate was used in the next step without further manipulation.

Provenance & Evidence