反应 #1857592

反应方程式

3-Chloro-4-(methylsulfonyl)thiophene-2-carbonyl chloride

triethylamine

((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-amine hydrochloride

1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-amine hydrochloride

→

3-chloro-N-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-4 (methylsulfonyl)thiophene-2-carboxamide

收率 45.2%

溶剂

CH3CN

DCM

反应条件

后处理

1. 1
   其他were in solution (˜10 minutes)
2. 2
   其他The ice bath was removed
3. 3
   workup.STIRRINGthe mixture was stirred for 2 hours
4. 4
   workup.ADDITIONThe reaction was diluted with dichloromethane (100 mL)
5. 5
   洗涤the organic phase was washed with H2O (200 mL)
6. 6
   干燥The organic layer was dried over sodium sulfate
7. 7
   过滤filtered
8. 8
   浓缩concentrated under reduced pressure
9. 9
   其他The solid was triturated with ethyl acetate/hexanes (1/5)

实验过程

To a stirring mixture of ((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-amine hydrochloride (Example 4-1a) (500 mg, 2 mmol) in DCM (20 mL), cooled to 0° C. via an ice water bath, was added triethylamine (600 mg, 6 mmol). The mixture was stirred until all solids were in solution (˜10 minutes). 3-Chloro-4-(methylsulfonyl)thiophene-2-carbonyl chloride (543 mg, 2.1 mmol), in 2 mL CH3CN, was added via syringe to the free amine at 0° C. The ice bath was removed and the mixture was stirred for 2 hours. The reaction was diluted with dichloromethane (100 mL) and the organic phase was washed with H2O (200 mL). The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. The solid was triturated with ethyl acetate/hexanes (1/5) to afford 3-chloro-N-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-4 (methylsulfonyl)thiophene-2-carboxamide (375 mg, 45%) as a white solid. 1H NMR (CDCl3, 400 MHz): δ 2.20 (s, 3H), 2.43 (s, 4H), 3.22 (s, 3H), 5.05 (s, 2H), 7.57 (s, 1H), 7.94 (s, 1H), 8.41 (s, 1H), 8.59 (bs, 1H). LC/MS; [M+H] 415.5. Melting point: 202-204° C.

来源