Diisopropylethylamine → N-(3-Hydroxy-4-(methoxyamino)-4-oxo-1-phenylbutan-2-yl)-2-(2-phenylthiazol-4-yl)nicotinamide

Participants

Reaction Conditions

Reaction Steps

DIPEA (200 μl, 0.567 mmol) was added to a suspension of 2-hydroxy-4-phenyl-3-(2-(2-phenylthiazol-4-yl)nicotinamido)butanoic acid (250 mg, 0.544 mmol) and O-methylhydroxylamine hydrochloride (90 mg, 1.078 mmol) in dichloromethane (50 ml) at 5° C. After about 5 min 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate (HATU) (665 mg, 1.748 mmol) was added, the pH adjusted to 8 via addition of further DIPEA, and the mixture then stirred for 1 h at 5° C. and then overnight at room temperature. Then dichloromethane (50 ml) was added, washed 2× with 10 ml of water and brine, dried, filtered and concentrated to give 430 mg of the crude product which was purified by chromatography on silica gel (dichloromethane+11-12% methanol. Concentration of the combined fractions and drying afforded 224 mg of a white amorphous solid;

Provenance & Evidence