1-((Pyrrolidine-1-carbonyl)methyl)piperazine → HCID 86624984, compound

Participants

Reaction Steps

N-(2-t-Butoxycarbonylaminophenyl)-4-(3-cyano-5-formylpyridin-2-yl)benzamide (0.3 g, prepared as described in Method 15 below) and 1-(pyrrolidinocarbonylmethyl)piperazine (0.14 g) were dissolved in dichloromethane (10 ml). Sodium triacetoxyborohydride (0.15 g) was added, and the mixture stirred for 3 hours before being washed with water (10 ml). The organic residues were separated and purified using flash column chromatography eluting with ethyl acetate, followed by (6-8%) MeOH in dichloromethane to give t-butyl (2-{[4-(3-cyano-5-{[4-(2-oxo-2-pyrrolidin-1-ylethyl)piperazin-1-yl]methyl}pyridin-2-yl)benzoyl]amino}phenyl)carbamate (300 mg) as a pale yellow oil. The oil was dissolved in methanol (10 ml), and a 4M solution of hydrogen chloride in 1,4-dioxan (10 ml) added and the solution stirred at ambient temperature for 2 hours. The solvent was evaporated, methanol (5 ml) added and the resulting solution absorbed onto an SCX-2 column, which was then washed with methanol (2 column volumes) and the product eluted with a 2M solution of ammonia in methanol (2 column volumes). The ammonia/methanol was evaporated to give a foam. This was treated with diethyl ether (20 ml), stirred and filtered to give the product as a white solid (195 mg, 57%); NMR Spectrum: (DMSO-d6 373K) 1.82 (m, 4H), 2.50 (m, 8H), 3.11 (s, 2H), 3.40 (m, 4H), 3.66 (s, 2H), 4.74 (br s, 2H), 6.64 (m, 1H), 6.82 (m, 1H), 6.98 (m, 1H), 7.27 (m, 1H), 7.99 (d, 2H), 8.13 (d, 2H), 8.24 (d, 1H), 8.87 (d, 1H), 9.49 (br s, 1H); Mass Spectrum: M+H+ 524.

Provenance & Evidence