1,2-Dichloroethane → [(2R)-2-(cyclopentylmethyl)-3-(2-{5-fluoro-2-methyl-6-[(3S)-3-methyl-4-morpholinyl]-4-pyrimidinyl}hydrazino)-3-oxopropyl]hydroxyformamide

Participants

Reaction Steps

To a solution of (3S)-4-(5-fluoro-6-hydrazino-2-methyl-4-pyrimidinyl)-3-methylmorpholine (0.2123 g, 0.880 mmol) in DMF (4 mL) was added (2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoic acid, N,N-diisopropylethylamine salt, isopropanol solvate (327.1 mg, 0.661 mmol), N-methylmorpholine (0.290 ml, 2.64 mmol), 1-hydroxy-7-azabenzotriazole (0.108 g, 0.794 mmol), and EDC (0.152 g, 0.793 mmol). The solution was stirred overnight, and then purified directly by Gilson RPLC. To a solution of the residue in MeOH (7 mL) was added 10% Pd/C (50% water, 88 mg). The mixture was hydrogenated under balloon pressure for 1 h, and then filtered through a PTFE membrane. The resulting solution was concentrated in vacuo, dissolved in EtOAc, and concentrated in vacuo. The solid was collected by vacuum filtration and washed with hexanes to give [(2R)-2-(cyclopentylmethyl)-3-(2-{5-fluoro-2-methyl-6-[(3S)-3-methyl-4-morpholinyl]-4-pyrimidinyl}hydrazino)-3-oxopropyl]hydroxyformamide (0.2326 g, 80% yield) as a white solid. LCMS: (M+H)+: 439.2.

Provenance & Evidence