1-BOC-3-Aminopiperidine → HCID 68872883, compound

Participants

Reaction Conditions

Reaction Steps

To a degassed solution of 1-amino-6-bromoisoquinolin (554 mg), prepared as described in WO 98/47876 (Akzo Nobel N.V.), 3-aminopiperidine-1-carboxylic acid tert-butyl ester (823 mg), 2-(di-tert-butylphosphino)biphenyl and sodium tert-butoxide (367 mg) in dioxane (10 ml) under argon, was added tris(dibenzylidene-acetone)dipalladium(0). The mixture was further degassed with argon then heated at 120° C. for 90 minutes. The mixture was cooled to room temperature then diluted with methanol. The crude mixture was loaded onto a pre-acidified SCX column and the basic products eluted with 2M ammonia in methanol to give a crude residue (700 mg). The residue was purified by preparative HPLC to give 3-(1-aminoisoquinolin-6-ylamino)piperidin-1-carboxylic acid tert-butyl ester. A mixture of the 3-(1-aminoisoquinolin-6-ylamino)-piperidin-1-carboxylic acid tert-butyl ester in dichloromethane (6 ml) and trifluoroacetic acid (3 ml) were stirred at ambient temperature for 3 h. The mixture was concentrated then purified by preparative HPLC followed by loading onto a pre-acidified SCX column and the free base eluted with 2M ammonia in methanol to give 6-(piperidin-3-ylamino)-isoquinolin-1-ylamine, El-MS: m/z=243.7 [M+H]+.

Provenance & Evidence