반응 #90773

반응 방정식

O-Methylhydroxylamine hydrochloride

diisopropylethlyamine

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

1-hydroxybenzotriazole

N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide

→

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

수율 94.3%

용매

acetic acid

Water

N,N-dimethylformamide

반응 조건

후처리

1. 1
   workup.STIRRINGthe solution stirred for additional 15 minutes
2. 2
   workup.ADDITIONwas added dropwise
3. 3
   workup.STIRRINGThe reaction mixture was stirred overnight tat the room temperature
4. 4
   추출The solution was extracted 2×2 L of ethyl acetate
5. 5
   세척The organic was washed with water (1 L), brine
6. 6
   건조dried over MgSO4
7. 7
   여과filtered
8. 8
   기타evaporated

실험 절차

To a solution of 2-[(5-chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]benzoic acid (67 g, 174 mmol) and 1-hydroxybenzotriazole (29.3 g, 191 mmol) in N,N-dimethylformamide (700 mL) was added N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide (36.6 g, 191 mmol) and the solution was stirred for 30 minutes. O-Methylhydroxylamine hydrochloride (15.95 g, 191 mmol) was added and the solution stirred for additional 15 minutes, the cooled down to the 0° C. and diisopropylethlyamine (91 mL, 521 mmol) was added dropwise. The reaction mixture was stirred overnight tat the room temperature. Water (4000 mL) was added and the solution was acidified with acetic acid (20 mL). The solution was extracted 2×2 L of ethyl acetate. The organic was washed with water (1 L), brine, and dried over MgSO4, filtered and evaporated. 2-[(5-Chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]-N-(methyloxy)benzamide (74 g, 164 mmol, 94% yield, 92% pure) was isolated as a yellow foam. 1H NMR (400 MHz, DMSO-d6) ppm 1.27 (d, J=6.57 Hz, 6H) 2.10 (s, 3 H) 3.71 (s, 3 H) 4.39 (quin, J=6.51 Hz, 1 H) 5.93 (s, 1 H) 6.66 (s, 1 H) 7.08-7.19 (m, 1 H) 7.49-7.64 (m, 3 H) 7.98 (s, 1 H) 8.50 (s, 1 H) 9.50 (s, 1 H) 11.93 (s, 1 H).; HPLC Rt=2.13 min, MS (ESI): [M+H]+=415.1.

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