反応 #90774

反応方程式

HCl

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

HCl

diethyl ether

→

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

収率 198.3%

溶媒

ethyl acetate

反応条件

後処理

1. 1
   その他to afford a cloudy solution
2. 2
   ろ過The cloudy solution was filtered
3. 3
   ろ過Product was collected by filtration
4. 4
   洗浄rinsed with ethyl acetate (2×500 mL each)
5. 5
   その他The wet cake was dried at 50-55° C./<5 mm Hg for 16-20 hours to a constant weight

実験手順

2-[(5-Chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]-N-(methyloxy)benzamide (235.2 g total weight, 228.0 g assayed content, 549.5 mmoles) was slurried in ethyl acetate (7.1 L, 30 volumes). The mixture was heated to about 50-55° C. to afford a cloudy solution. The cloudy solution was filtered. To the filtered solution was added 2.0 M HCl in diethyl ether (210 g, 281 mL, 1.02 equiv.) over 15-20 minutes. Upon HCl addition, a white slurry was observed. It was stirred at room temperature for about 16-20 hours. Product was collected by filtration and rinsed with ethyl acetate (2×500 mL each). The wet cake was dried at 50-55° C./<5 mm Hg for 16-20 hours to a constant weight. 2-[(5-Chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]-N-(methyloxy)benzamide, monohydrochloride, (245.9 g, 544.7 mmoles, 96% yield) was isolated as a white solid. 1H NMR (400 MHz, DMSO-d6) ppm 1.32 (d, J=6.57 Hz, 6 H) 2.18 (s, 3 H) 3.70 (s, 3 H) 4.35-4.62 (m, 1 H) 6.12 (br. s, 1 H) 6.60 (br. s, 1 H) 7.19-7.41 (m, 1 H) 7.48-7.75 (m, 3 H) 8.09 (s, 1 H) 9.59-9.99 (m, 2 H) 11.98 (br. s, 1 H). C18 HPLC RT=6.1 minutes (99.6% purity). MS (ESI): 414.8 [M+H]+.

出典