Hydrochloric Acid → HCID 178457792, compound

Participants

Reaction Steps

A suspension of cis-4-((E)-6-((4-((tert-butoxycarbonylamino)methyl)piperidin-1-yl)methyl)-2-(4-fluorobenzoylimino)-2,3-dihydro-1H-benzo[d]imidazol-1-yl)cyclohexanecarboxylic acid (0.57 g, 0.94 mmol) in thionyl chloride (6.85 mL, 94 mmol) under nitrogen atmosphere was stirred for 30 minutes at RT and then concentrated to dryness. The residue was suspended in THF (9.4 mL) and cooled in an ice bath under nitrogen atmosphere. To the resulting mixture was added isopropylamine (0.804 mL, 9.38 mmol) as a solution in THF (1 mL). The ice bath was removed and the mixture was stirred for 1 hour at RT. The resulting mixture was diluted with water (10 mL) and the aqueous layer extracted with DCM (30 mL). The organic layer was dried over sodium sulfate and concentrated to dryness under high vacuum to afford a tan solid. The solid was suspended in HCl (4.0M in dioxanes) (23.45 mL, 94 mmol) and stirred for 16 hours. The mixture was concentrated, suspended in DCM and washed with aqueous NaHCO3 solution. The organic portion was collected, dried over sodium sulfate, and concentrated to dryness under high vacuum to afford a tan solid. The solid was purified by silica gel chromatography (1-10% MeOH/DCM (1% NH4OH)) to afford (E)-N-(6-((4-(aminomethyl)piperidin-1-yl)methyl)-1-(cis-4-(isopropylcarbamoyl)cyclohexyl)-1H-benzo[d]imidazol-2(3H)-ylidene)-4-fluorobenzamide (0.3 g, 58.3% yield). MS m/z=549.2 [M+H]. Calc'd for C31H41FN6O2: 548.3.

Provenance & Evidence