4-Hydroxybenzaldehyde → HCID 86756689, compound

Participants

Reaction Conditions

Reaction Steps

(S)-N-(2-chloro-6-methylbenzoyl)-4-[[(2-piperidinyl)carbonyl]amino]-L-phenylalanine methyl ester hydrochloride (100 mg, 0.2 mmol), DIPEA (0.10 mL, 0.54 mmol) and 4-hydroxybenzaldehyde (30 mg, 0.25 mmol) was added to a suspension of activated 3 Å molecular sieves (100 mg) in THF (1.5 mL). The resulting mixture was stirred room temperature overnight and at 60° C. for 3 hr. After it was cooled to room temperature, the mixture was transferred onto a silica gel column and eluted with ethyl acetate:hexane (2:1) to give N-[(2-chloro-6-methylphenyl)carbonyl]]-4-[(8aS)-hexahydro-3-(4-hydroxyphenyl)-1-oxoimidazo[1.5-a]pyridin-2-yl]-L-phenylalanine methyl ester (17.5 mg, 0.031 mmol) as a foam. The methyl ester (17.5 mg, 0.031 mmol) was hydrolyzed with 1N NaOH (0.1 mL, 0.1 mmol) in 0.5 mL of ethanol at room temperature for 6 hr. The reaction mixture was acidified to pH<2 with TFA and was purified on RP-HPLC to give N-[(2-chloro-6-methylphenyl)carbonyl]-4-[(8aS)-hexahydro-3-(4-hydroxyphenyl)-1-oxoimidazo[1.5-a]pyridin-2-yl]-L-phenylalanine (8.3 mg, 0.015 mmol), in 7.5% yield. HRMS: calcd. 548.1952. Obs. 548.1938 (M+H).

Provenance & Evidence