Reacción #1513132

Ecuación de reacción

HATU

(R)-2-amino-N-(1-hydroxy-3,3-dimethyl-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)-4-(4-(trifluoromethyl)phenyl)butanamide

Boc-Glu(OBzl)-OH

DIPEA

→

(S)-benzyl 4-(tert-butoxycarbonylamino)-5-((R)-1-(1-hydroxy-3,3-dimethyl-1,3-dihydrobenzo[c][1,2]oxaborol-6-ylamino)-1-oxo-4-(4-(trifluoromethyl)phenyl)butan-2-ylamino)-5-oxopentanoate

Rendimiento 93.0%

Disolventes

DCM

Condiciones de reacción

Tratamiento posterior

1. 1
   LavadoThe mixture was washed with 2 N aqueous HCl, 1 M aqueous K2CO3, brine
2. 2
   Secadodried over MgSO4
3. 3
   OtroThe solution was evaporated to dryness under vacuum

Procedimiento

To a suspension of (R)-2-amino-N-(1-hydroxy-3,3-dimethyl-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)-4-(4-(trifluoromethyl)phenyl)butanamide (CLXIX) (1.2 g, 2.71 mmol) and Boc-Glu(OBzl)-OH (CLXX) (0.915 g, 2.71 mmol) in DCM (10 mL) was added DIPEA (1.39 mL, 8.13 mmol). To this solution was added HATU (1.03 g, 2.71 mmol) and the mixture was stirred at room temperature overnight. The mixture was washed with 2 N aqueous HCl, 1 M aqueous K2CO3, brine and dried over MgSO4. The solution was evaporated to dryness under vacuum to give (S)-benzyl 4-(tert-butoxycarbonylamino)-5-((R)-1-(1-hydroxy-3,3-dimethyl-1,3-dihydrobenzo[c][1,2]oxaborol-6-ylamino)-1-oxo-4-(4-(trifluoromethyl)phenyl)butan-2-ylamino)-5-oxopentanoate as an orange foam (1.83 g, 2.52 mmol, 93% yield). 1H NMR (DMSO-d6) δ ppm 1.33 (s, 9H), 1.4 (s, 6H), 1.8-1.88 (m, 1H), 1.9-1.96 (m, 2H), 2.08 (brs, 1H), 2.42 (brs, 2H), 2.6-2.66 (m, 1H), 2.7-2.76 (m, 1H), 3.98-4.05 (m, 1H), 4.4 (brs, 1H), 5.07 (s, 2H), 7.1 (brs, 1H), 7.28-7.34 (m, 6H), 7.37-7.44 (m, 2H), 7.55-7.63 (m, 3H), 7.89 (s, 1H), 8.34 (brs, 1H), 9.0 (s, 1H), 9.86 (s, 1H); 19F NMR (DMSO-d6) δ ppm −60.11 (s, 3F); ESIMS found for C37H43BF3N3O8 m/z 726.7 (M+H).

Fuente