تفاعل #1857592

معادلة التفاعل

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

المردود 45.2%

المذيبات

CH3CN

DCM

ظروف التفاعل

المعالجة

1. 1
   أخرىwere in solution (˜10 minutes)
2. 2
   أخرىThe 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
   غسيلthe organic phase was washed with H2O (200 mL)
6. 6
   تجفيفThe organic layer was dried over sodium sulfate
7. 7
   ترشيحfiltered
8. 8
   تركيزconcentrated under reduced pressure
9. 9
   أخرىThe solid was triturated with ethyl acetate/hexanes (1/5)

الإجراء التجريبي

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.

المصدر