Chloroacetyl chloride → 1-(4-Benzylpiperidinecarbonyl)methyl-5-cyanobenzimidazole

Participants

Reaction Steps

(4-Benzylpiperidinecarbonyl)methylene chloride was prepared by acylation of 4-benzylpiperidine (100 mmol) with a-chloroacetyl chloride (100 mmol) in THF (250 mL) and K2CO3 (100 mL. Alkylation of 5-cyanobenzimidazole (2 mmol) with (4-benzylpiperidinecarbonyl)methylene chloride (2 mmol) in DMF (5 mL) in the presence of NaH (3 mmol) at from 0° C. to room temperature over 16 hours, followed by purification on TLC plates gave 1-(4-benzylpiperidinecarbonyl)methyl-6-cyanobenzimidazole and 1-(4-benzylpiperidinecarbonyl)methyl-5-cyanobenzimidazole (0.4 g, 56% of yield). This mixture (1.11 mmol) was then carried through the Pinner reaction, followed by purification on TLC plates with 10% MeOH in CH2Cl2, and further purification by HPLC to give the title compounds: MP: 54-56° C.; MS: 376.4 (M+H)+ ; HRMS:376.2118 (obs.), 376.2137 (calcd.); Anal.: (C22H25N5O1 +1.8TFA+0.1 HCl).

Provenance & Evidence