Diisopropylethylamine → Ethyl 4-(2-bromo-4-fluorophenyl)-6-(((S)-3-(hydroxycarbamoyl)morpholino)methyl)-2-(thiazol-2-yl)-1,4-dihydropyrimidine-5-carboxylate

Participants

Reaction Conditions

Reaction Steps

A solution of (3S)-4-(((6-(2-bromo-4-fluorophenyl)-5-(ethoxycarbonyl)-2-(thiazol-2-yl)-3,6-dihydropyrimidin-4-yl)methyl)morpholine-3-carboxylic acid (0.74 g, 1.36 mmol), EDC.HCl (0.31 g, 1.62 mmol), HOAt (185 mg, 1.36 mmol) and DIPEA (210 mg, 1.62 mmol) in DCM (20 mL) was stirred at −10° C. for 30 minutes. Then to the mixture was added a solution of O-(tert-butyldimethylsilyl)hydroxylamine (0.2 g, 1.36 mmol) in DCM (2.0 mL) slowly at −10° C. Then the mixture was warmed to 25° C. and stirred for 12 hours. The mixture was concentrated in vacuo and the residue was dissolved in a solution of HCl in EtOAc (6 mol/L, 10 mL), then the mixture was stirred at 25° C. for 2 hours. The reaction mixture was diluted with EtOAc (200 mL) and water (100 mL), and the mixture was adjusted to pH 7 with aqueous ammonia. The organic layer was dried over Na2SO4, and concentrated in vacuo. The residue was purified by a silica gel column chromatography (DCM/MeOH (V/V)=30/1) to give the title compound as a yellow solid (0.05 g, 6.5%). The compound was characterized by the following spectroscopic data:

Provenance & Evidence