Reacción #90821

Ecuación de reacción

2-[(5-chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]-3-fluorobenzoic acid

HOBT

EDC

DIEA

→

2-[(5-Chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]-3-fluoro-N-(methyloxy)benzamide

Rendimiento 30.5%

Disolventes

acetic acid

Water

N,N-dimethylformamide

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.STIRRINGThe reaction mixture was stirred at the room temperature 24 hr
2. 2
   Extracciónthe solution was extracted with 2×50 ml of ethyl acetate
3. 3
   LavadoThe combined organic layers were washed with 2×50 ml
4. 4
   Secadodried over MgSO4
5. 5
   Otroevaporated
6. 6
   Filtraciónfiltered

Procedimiento

To a solution of 2-[(5-chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]-3-fluorobenzoic acid (3.2 g, 7.92 mmol) in N,N-dimethylformamide (DMF) (50 mL) was added HOBT (1.456 g, 9.51 mmol) and EDC (1.823 g, 9.51 mmol) and the reaction mixture was stirred for 30 min. To this solution was added O-methoxylamine hydrochloride (0.794 g, 9.51 mmol). After 30 min the reaction mixture was cooled to 0° C. and DIEA (4.14 mL, 23.77 mmol) was added. The reaction mixture was stirred at the room temperature 24 hr. Water (100 mL) was added followed by acetic acid (1 mL) and the solution was extracted with 2×50 ml of ethyl acetate. The combined organic layers were washed with 2×50 ml sat KHCO3, brine, dried over MgSO4 and evaporated. The oil was suspended in dichloromethane and filtered. 2-[(5-Chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]-3-fluoro-N-(methyloxy)benzamide (1.1 g, 2.414 mmol, 30.5% yield) was isolated as a white solid; 1H NMR (400 MHz, DMSO-d6) ppm 1.24 (d, J=6.57 Hz, 6 H) 2.08 (s, 3 H) 3.68 (s, 3 H) 4.33 (quin, J=6.57 Hz, 1 H) 5.83 (d, J=5.05 Hz, 1 H) 5.84 (s, 1 H) 7.30-7.49 (m, 2 H) 7.49-7.63 (m, 1 H) 7.92 (s, 1 H) 8.41 (d, J=4.29 Hz, 2 H) 11.85 (s, 1 H); HPLC Rt=2.18 min, MS (ESI): 433.3 [M+H]+.

Fuente