Reaktion #90773

Reaktionsgleichung

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

Ausbeute 94.3%

Lösungsmittel

acetic acid

Water

N,N-dimethylformamide

Reaktionsbedingungen

Aufarbeitung

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
   ExtraktionThe solution was extracted 2×2 L of ethyl acetate
5. 5
   WaschenThe organic was washed with water (1 L), brine
6. 6
   Trocknendried over MgSO4
7. 7
   Filtrationfiltered
8. 8
   Sonstigeevaporated

Vorschrift

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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