Triethylamine → (R)-6-(3-(3-(5-cyclopropyl-1,3,4-thiadiazol-2-yl)ureido)piperidin-1-yl)-2-(4-(morpholine-4-carbonyl)phenylamino)nicotinamide

Participants

Reaction Steps

A suspension of (R)-6-(3-aminopiperidin-1-yl)-2-(4-(morpholine-4-carbonyl)phenylamino)nicotinamide (40 mg, 0.094 mmol), phenyl 5-cyclopropyl-1,3,4-thiadiazol-2-ylcarbamate (29.5 mg, 0.113 mmol), and Et3N (0.016 mL, 0.113 mmol) in CH2Cl2 (2 mL) was stirred at rt overnight. The reaction mixture was diluted with CH2Cl2, washed with water, and concentrated. The residue was purified by prep-HPLC. The product containing fractions were collected, neutralized with saturated NaHCO3, extracted with CH2Cl2, separated, and concentrated to give 28 mg of (R)-6-(3-(3-(5-cyclopropyl-1,3,4-thiadiazol-2-yl)ureido)piperidin-1-yl)-2-(4-(morpholine-4-carbonyl)phenylamino)nicotinamide as a light pink solid. LCMS: (M+H)+=592.18. 1H NMR (400 MHz, CDCl3-MIX) δ ppm 11.09 (1H, s), 7.59 (2H, d, J=8.79 Hz), 7.55 (1H, d, J=9.23 Hz), 7.24-7.28 (2H, m), 6.04 (1H, d, J=8.79 Hz), 3.93 (1H, dd, J=13.18, 3.08 Hz), 3.73-3.86 (2H, m), 3.53 (7H, d, J=6.15 Hz), 3.31-3.41 (1H, m), 3.22-3.31 (2H, m), 2.11-2.21 (1H, m), 1.90-2.00 (1H, m), 1.67-1.79 (1H, m), 1.51-1.65 (2H, m), 1.03-1.12 (2H, m), 0.89-0.96 (2H, m).

Provenance & Evidence