反应详情

To a suspension of 1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylic acid (the product from Step B) (146 g, 500 mmol) in dichloromethane (approximately 2 L) was added N,N-dimethylformamide (20 drops) and oxalyl chloride (67 mL, 750 mmol) in approximately 5-mL portions over approximately 2 h. Vigorous gas evolution occurred during the addition. The reaction mixture was stirred at room temperature overnight. The reaction mixture was concentrated in vacuo to provide the crude acid chloride as an opaque orange mixture. This material was taken up in dichloromethane, filtered to remove some solids and the reconcentrated and used without further purification. The crude acid chloride was dissolved in acetonitrile (250 mL) and added to a suspension of the product from Step C in acetonitrile (400 mL). Pyridine (250 mL) was added, the mixture was stirred for 15 min at room temperature, then warmed to reflux for 3 h. The resulting mixture was cooled to room temperature and stirred overnight to provide a solid mass. Additional acetonitrile was added and the mixture was mixed to form a thick slurry. The solids were collected and washed with cold acetonitrile. The solids were air-dried and the dried in vacuo at 90° C. for 5 h to yield 144.8 g of fluffy white solid.

1. additionVigorous gas evolution occurred during the addition
2. concentrationThe reaction mixture was concentrated in vacuo
3. customto provide the crude acid chloride as an opaque orange mixture
4. filtrationfiltered
5. customto remove some solids
6. customthe reconcentrated and used without further purification
7. dissolutionThe crude acid chloride was dissolved in acetonitrile (250 mL)
8. additionadded to a suspension of the product from Step C in acetonitrile (400 mL)
9. additionPyridine (250 mL) was added
10. stirringthe mixture was stirred for 15 min at room temperature
11. temperaturewarmed
12. temperatureto reflux for 3 h
13. temperatureThe resulting mixture was cooled to room temperature
14. stirringstirred overnight
15. customto provide a solid mass
16. additionthe mixture was mixed
17. customto form a thick slurry
18. customThe solids were collected
19. washwashed with cold acetonitrile
20. customThe solids were air-dried
21. customthe dried in vacuo at 90° C. for 5 h