Ammonium Chloride → N-(5-Chloro-1,3-thiazol-2-yl)-3-cyano-N-(2,4-dimethoxybenzyl)-4-fluorobenzenesulfonamide

HRID 46296

반응식

HRID 46296 반응식
[Cl:1][C:2]1[S:6][C:5]([NH:7][CH2:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][C:10]=2[O:17][CH3:18])=[N:4][CH:3]=1.C[Si](C)(C)N[Si](C)(C)C.[Li].[C:29]([C:31]1[CH:32]=[C:33]([S:38](Cl)(=[O:40])=[O:39])[CH:34]=[CH:35][C:36]=1[F:37])#[N:30].[Cl-].[NH4+]>O1CCCC1.O>[Cl:1][C:2]1[S:6][C:5]([N:7]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][C:10]=2[O:17][CH3:18])[S:38]([C:33]2[CH:34]=[CH:35][C:36]([F:37])=[C:31]([C:29]#[N:30])[CH:32]=2)(=[O:39])=[O:40])=[N:4][CH:3]=1

참가 물질

7

반응물 4

HCID 25517Ammonium ChlorideHCID 27789083-Cyano-4-fluorobenzenesulfonyl chlorideHCID 57426343Lithium bis(trimethylsilyl)amideHCID 577321515-chloro-N-(2,4-dimethoxybenzyl)-1,3-thiazol-2-amine

생성물 1

HCID 59436479N-(5-Chloro-1,3-thiazol-2-yl)-3-cyano-N-(2,4-dimethoxybenzyl)-4-fluorobenzenesulfonamide수율 57%

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
-70 °C

실험 절차

Under an atmosphere of nitrogen, 5-chloro-N-(2,4-dimethoxybenzyl)-1,3-thiazol-2-amine (Preparation 208, 3.0 g 10.5 mmol) was dissolved in tetrahydrofuran (20 ml) and cooled to −70° C. Lithium hexamethyldisilazane (1 M in tetrahydrofuran, 12.6 ml, 12.6 mmol) was added dropwise, keeping the temperature below −60° C. After 5 minutes, the cooling bath was removed and the reaction warmed to room temperature, stirred for a further 5 minutes then cooled back to −70° C. 3-Cyano-4-fluorobenzenesulfonyl chloride (2.54 g, 11.6 mmol) in tetrahydrofuran (10 ml) was added dropwise keeping the temperature below −60° C. and the reaction mixture was warmed to room temperature. Saturated aqueous ammonium chloride solution (50 ml) was added followed by water to dissolve the solid which had precipitated out. The aqueous layer was extracted with ethyl acetate (50 ml) and the organic extracts dried over magnesium sulphate and decolourising charcoal, filtered through Celite™ and the filtrate evaporated in vacuo. The resulting gum was purified using a short column (silica gel, 150 g) eluting with ethyl acetate:heptane (1:1, by volume) affording a gum which was triturated with tert-butyl ether, filtered, washed with heptane and dried in vacuo to give the title compound as a buff solid, 2.84 g, 57% yield.

후처리

  1. customthe temperature below −60° C
  2. customthe cooling bath was removed
  3. temperaturethe reaction warmed to room temperature
  4. temperaturethen cooled back to −70° C
  5. customthe temperature below −60° C.
  6. temperaturethe reaction mixture was warmed to room temperature
  7. dissolutionto dissolve the solid which
  8. customhad precipitated out
  9. extractionThe aqueous layer was extracted with ethyl acetate (50 ml)
  10. dry with materialthe organic extracts dried over magnesium sulphate
  11. filtrationfiltered through Celite™
  12. customthe filtrate evaporated in vacuo
  13. customThe resulting gum was purified
  14. washeluting with ethyl acetate:heptane (1:1, by volume)
  15. customaffording a gum which
  16. customwas triturated with tert-butyl ether
  17. filtrationfiltered
  18. washwashed with heptane
  19. customdried in vacuo

출처 및 근거

ORD 기록
ord-2d8a4c236074466fa5095d418d783941
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08541588B2

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