반응 #1857592

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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

수율 45.2%

용매

CH3CN

DCM

반응 조건

후처리

1. 1
   기타were in solution (˜10 minutes)
2. 2
   기타The 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
   세척the organic phase was washed with H2O (200 mL)
6. 6
   건조The organic layer was dried over sodium sulfate
7. 7
   여과filtered
8. 8
   농축concentrated under reduced pressure
9. 9
   기타The solid was triturated with ethyl acetate/hexanes (1/5)

실험 절차

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.

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