Reacción #811566

Ecuación de reacción

K2CO3

N-methyl-N-(3-styryl-1H-indazol-6-yl)-benzene-1,3-diamine

5-methyl-thiazole-2-carboxylic acid

HATU

→

title compound

5-Methyl-thiazole-2-carboxylic acid {3-[methyl-(3-styryl-1H-indazol-6-yl)-amino]-phenyl}-amide

Disolventes

DMF

EtOAc

CH2Cl2 EtOAc

CH2Cl2 EtOAc

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroThe reaction was quenched with saturated NaHCO3(aq) (2 mL)
2. 2
   workup.ADDITIONthen diluted with EtOAc (15 mL)
3. 3
   Lavadothe organic phase was washed with brine (3 mL)
4. 4
   Otrodecanted
5. 5
   Concentraciónconcentrated under reduced pressure
6. 6
   Lavadothe organic phase was washed with brine (3 mL)
7. 7
   Otrodecanted
8. 8
   Concentraciónconcentrated under reduced pressure to a solid
9. 9
   OtroThe crude material was purified by silica gel chromatography (eluting with CH2Cl2:EtOAc 85:15)

Procedimiento

To a solution of N-methyl-N-(3-styryl-1H-indazol-6-yl)-benzene-1,3-diamine, prepared in Example 11, (26 mg, 0.075 mmol) and 5-methyl-thiazole-2-carboxylic acid (64 mg, 0.45 mmol) in DMF (0.375 mL) at 23° C. under an atmosphere of argon was added HATU (171 mg, 0.45 mmol). After 1 h, TLC analysis (CH2Cl2:EtOAc 8:2) indicated no starting material. The reaction was quenched with saturated NaHCO3(aq) (2 mL) then diluted with EtOAc (15 mL) and the organic phase was washed with brine (3 mL), decanted and concentrated under reduced pressure. The oil was suspended in MeOH (2 mL) and K2CO3 (62 mg, 0.45 mmol) was added. The resulting mixture was stirred at 23° C. under an atmosphere of argon. After 1 h TLC analysis (CH2Cl2:EtOAc 8:2) indicated no starting material. The reaction was diluted with EtOAc (15 mL) and the organic phase was washed with brine (3 mL), decanted and concentrated under reduced pressure to a solid. The crude material was purified by silica gel chromatography (eluting with CH2Cl2:EtOAc 85:15) to give the title compound after purification by semi-prep. HPLC (9.9 mg, 28%). Rf sm 0.25, Rf p 0.39 (hexane:EtOAc 8:2); LCMS (ESI+) [M+H]/z Calc'd 466. found 466. Anal. Calc'd C, (69.65); H, (4.98); N, (15.04); S, (6.89). Found: C, (69.24); H, (5.35); N, (13.97); S, (5.95).

Fuente