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Carbon Disulfide → 5-(Methylthio)-8-(3-(trifluoromethyl)phenyl)-3H,6H-1,4,5a,8a-tetraazaacenaphthylen-3-one

HRID 6218
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HRID 6218 반응식
[F:1][C:2]([F:22])([F:21])[C:3]1[CH:4]=[C:5]([C:9]2[N:14]3[N:15]=[CH:16][C:17]([C:18]([NH2:20])=[O:19])=[C:13]3[NH:12][CH2:11][CH:10]=2)[CH:6]=[CH:7][CH:8]=1.[CH3:23]C(C)([O-])C.[K+].[C:29](=[S:31])=S>O1CCCC1>[CH3:23][S:31][C:29]1[N:12]2[C:13]3[N:14]([C:9]([C:5]4[CH:6]=[CH:7][CH:8]=[C:3]([C:2]([F:21])([F:1])[F:22])[CH:4]=4)=[CH:10][CH2:11]2)[N:15]=[CH:16][C:17]=3[C:18](=[O:19])[N:20]=1
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참가 물질

5

반응물 3

HCID 6348Carbon DisulfideHCID 27370934,5-Dihydro-7-[3-(trifluoromethyl)phenyl]pyrazolo[1,5-a]pyrimidine-3-carboxamideHCID 23665647Potassium tert-butoxide

생성물 1

HCID 98853995-(Methylthio)-8-(3-(trifluoromethyl)phenyl)-3H,6H-1,4,5a,8a-tetraazaacenaphthylen-3-one수율 90.5%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
-6.199999809265137 °C

실험 절차

A solution of 3.18 kg of 4,5-dihydro-7-[3-(trifluoromethyl)-phenyl]pyrazolo[1,5-a]pyrimidine-3-carboxamide in 30 L of tetrahydrofuran is cooled to 2.8° C. under nitrogen and stirred while 1370 g of potassium tert-butoxide is added portionwise over 25 minutes while maintaining a temperature less than 4° C. The reaction mixture is stirred at -6.2° C. for 45 minutes. To the reaction mixture is added 850 g of carbon disulfide through a dropping funnel over a 10 minute period while maintaining the temperature below 2° C. The funnel is rinsed with 500 ml of tetrahydrofuran and the reaction mixture allowed to stir for 45 minutes. While maintaining the temperature from -8° C. to 3.2° C.. 1870 g of methyl iodide is added dropwise through a dropping funnel. The funnel is rinsed with 500 ml of tetrahydrofuran and the reaction mixture allowed to stir for 1 hour. An additional 3804 g of methyl iodide is added. The reaction mixture is stirred for 50 minutes while cooling to -23.1° C. An additional 2530 g of potassium tert-butoxide is added over 2 hours while maintaining a temperature of -23.1° C. to 10.0° C. After half of the potassium tert-butoxide is added another 300 ml of methyl iodide is added. The remaining potassium tert-butoxide is added and the reaction mixture stirred while warming to room temperature overnight. The reaction mixture is diluted with 3 kg of ice and 10 L of water then added to 80 L of water with stirring. The reaction flask is rinsed with 26 L of water which is added to the ice and water containing the original reaction mixture. Stirring is continued for 40 minutes and the solids collected by filtration. The filter cake is washed with 20 L of water and dried at 30 mm Hg, 35° C. to afford 3.4 kg (90%) of the desired product.

후처리

  1. additionis added portionwise over 25 minutes
  2. temperaturewhile maintaining a temperature less than 4° C
  3. temperaturewhile maintaining the temperature below 2° C
  4. washThe funnel is rinsed with 500 ml of tetrahydrofuran
  5. stirringto stir for 45 minutes
  6. temperatureWhile maintaining the temperature from -8° C. to 3.2° C.
  7. addition1870 g of methyl iodide is added dropwise through a dropping funnel
  8. washThe funnel is rinsed with 500 ml of tetrahydrofuran
  9. stirringto stir for 1 hour
  10. additionAn additional 3804 g of methyl iodide is added
  11. stirringThe reaction mixture is stirred for 50 minutes
  12. temperaturewhile cooling to -23.1° C
  13. additionAn additional 2530 g of potassium tert-butoxide is added over 2 hours
  14. temperaturewhile maintaining a temperature of -23.1° C. to 10.0° C
  15. additionAfter half of the potassium tert-butoxide is added another 300 ml of methyl iodide
  16. additionis added
  17. additionThe remaining potassium tert-butoxide is added
  18. stirringthe reaction mixture stirred
  19. temperaturewhile warming to room temperature overnight
  20. additionThe reaction mixture is diluted with 3 kg of ice and 10 L of water
  21. additionthen added to 80 L of water
  22. stirringwith stirring
  23. washThe reaction flask is rinsed with 26 L of water which
  24. additionis added to the ice and water containing the original reaction mixture
  25. stirringStirring
  26. waitis continued for 40 minutes
  27. filtrationthe solids collected by filtration
  28. washThe filter cake is washed with 20 L of water
  29. customdried at 30 mm Hg, 35° C.

출처 및 근거

ORD 기록
ord-5669067be2dd44efab57c051c34b17f5
출처 데이터셋
uspto-grants-1993_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US05247086

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