Reaction #11083

Reaction equation

intermediate 25a

(S)-3-{[(benzyloxy)carbonyl][3-(trifluoromethyl)benzyl]amino}-4-oxo-4,6,7,8-tetrahydropyrrolo[1,2-a]pyrimidine-6-carboxylic acid

[(4-aminomethyl-phenyl)-imino-methyl]-carbamic acid tert-butyl ester

NaHCO3

HOAT

EDCI

→

intermediate 25b

Yield 79.2%

benzyl (S)-{6-[4-(tert-Butoxycarbonylamino-imino-methyl)-benzylcarbamoyl]-4-oxo-4,6,7,8-tetrahydro-pyrrolo[1,2-a]pyrimidin-3-yl}-(3-trifluoromethyl-benzyl)-carbamate

Yield 79.2%

Solvents

EtOAc

CH2Cl2 DMF

Conditions

Workup

1. 1
   WashThe organic phase was washed with H2O, 1N HCl, H2O, and sat. NaHCO3, and brine
2. 2
   Dryingdried (Na2SO4) and brine
3. 3
   OtherThe crude residue was triturated with Et2O

Procedure

To a solution of intermediate 25a (0.281 mmol) and [(4-aminomethyl-phenyl)-imino-methyl]-carbamic acid tert-butyl ester (84 mg, 0.337 mmol) in 3 mL 5:1 CH2Cl2/DMF at 0° C., were added NaHCO3 (59 mg, 0.703 mmol), HOAT (42.1 mg, 0.309 mmol), and EDCI (75.5 mg, 0.393 mmol). The mixture was allowed to warm to rt and stir 20 h, then was diluted with EtOAc. The organic phase was washed with H2O, 1N HCl, H2O, and sat. NaHCO3, and brine, dried (Na2SO4) and brine. The crude residue was triturated with Et2O to afford 160 mg (79%) of intermediate 25b as a white solid. MS (ESI) 719.4 (M+H+).

Source