Reaktion #90818

Reaktionsgleichung

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

HOBT

DIEA

EDC

→

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

Ausbeute 48.8%

Lösungsmittel

N,N-dimethylformamide

acetic acid

Water

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.WAITafter 30 min
2. 2
   Sonstigeat 0° C
3. 3
   workup.STIRRINGThe reaction mixture was stirred at room temperature 24 hr
4. 4
   Extraktionthe solution extracted with 2×50 ml of ethyl acetate
5. 5
   SonstigeThe organic layer was separated
6. 6
   Waschenwashed with 2×50 ml
7. 7
   Trocknendried over MgSO4
8. 8
   Sonstigeevaporated
9. 9
   Filtrationfiltered

Vorschrift

To the solution of 2-[(5-chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]-5-fluorobenzoic acid (1128 mg, 2.79 mmol) in N,N-dimethylformamide (DMF) (20 mL) was added HOBT (513 mg, 3.35 mmol) followed by EDC (643 mg, 3.35 mmol) and the reaction mixture stirred for 30 min. To this solution was added o-methoxylamine hydrochloride (280 mg, 3.35 mmol) and after 30 min, at 0° C. DIEA (1.460 mL, 8.38 mmol) was added. The reaction mixture was stirred at room temperature 24 hr. Water (100 mL) was added followed by acetic acid (1 mL) and the solution extracted with 2×50 ml of ethyl acetate. The organic layer was separated, washed with 2×50 ml sat KHCO3, brine, dried over MgSO4 and evaporated. The resulting oil was suspended in dichloromethane and filtered. 2-[(5-Chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]-5-fluoro-N-(methyloxy)benzamide (620 mg, 1.361 mmol, 48.7% yield) was isolated as a white solid. 1H NMR (400 MHz, DMSO-d6) ppm 1.26 (d, J=6.57 Hz, 6 H) 2.10 (s, 3 H) 3.69 (s, 3 H) 4.38 (quin, J=6.57 Hz, 1 H) 5.92 (s, 1 H) 6.50 (s, 1 H) 7.41-7.52 (m, 2 H) 7.58 (dd, J=8.72, 4.67 Hz, 1 H) 7.96 (s, 1 H) 8.46 (s, 1 H) 9.10 (s, 1 H) 11.95 (s, 1 H); HPLC Rt=2.24 min, MS (ESI): 433.4 [M+H]+.

Quelle