Dimethylformamide → HCID 22490316, compound

Participants

Reaction Steps

The synthesis is comprised of the following steps: (a) a solution of 2-(S)-methylpyrrolidine hydrobromide 20 in dimethylformamide is treated with triethylamine followed by a solution of 2-tert-butoxycarbonylamino-3-methylbutyric acid 2,5-dioxo-pyrrolidin-1-yl 12 in dimethylformamide to yield (1-(2-methylpyrrolidine-1-carbonyl)-2-methyl-propyl)-carbamic acid tert-butyl ester 21; which is then (b) dissolved in methylene chloride, or any suitable solvent, and treated with trifluoroacetic acid to yield 2-amino-1-(2-methylpyrrolidin-1-yl)-3-methylbutan-1-one 22; (c) a solution of 22 in dimethylformamide is treated with triethylamine followed by a solution of 8 in dimethylformamide to yield 3-(1-(2-(S)-methylpyrrolidine-1-carbonyl)-2-(S)-methylpropyl-carbamoyl)-octanoic acid tert-butyl ester 23; (d) treatment of 23 in dichloromethane with trifluoroacetic acid to yield 3-(1-(2-methyl-pyrrolidine-1-carbonyl)-2-methyl-propylcarbamoyl)-octanoic acid 24; (e) treatment of a solution 24 and hydroxysuccinamide 7 with dicyclohexylcarbodiimide to afford 3-(1-(2-methyl-pyrrolidine-1-carbonyl)-2-methylpropylcarbamoyl)-octanoic acid 2,5-dioxo-pyrrolidin-1-yl ester 25; (f) treatment of a suspension of O-benzylhydroxyamine hydrochloride 18 in dimethylformamide with triethylamine followed by a solution of 25 in dimethylformamide to afford N4-benzyloxy-N1-(1-(2-benzyloxymethyl-pyrrolidine-1-carbonyl)-2-methyl-propyl)-2-pentyl-succinamide 26. (g) hydrogenating 26 with hydrogen gas and palladium in activated carbon wherein N4-hydroxy-N1-(1-(2-methyl-pyrrolidine-1-carbonyl)-3-methyl-propyl)-2-pentyl-succinamide 27 is thereby formed.

Provenance & Evidence