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Water → N-tert-butyl-2-{1-[4-(4-chloro-phenyl)-6-methyl-pyrimidin-2-yl]-1H-imidazol-4-yl}-thiazole-5-sulfonamide

HRID 1928211
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HRID 1928211 반응식
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[C:12]([CH3:14])[N:11]=[C:10]([N:15]3[CH:19]=[C:18]([Sn](CCCC)(CCCC)CCCC)[N:17]=[CH:16]3)[N:9]=2)=[CH:4][CH:3]=1.[C:33]([NH:37][S:38]([C:41]1[S:45][C:44](Cl)=[N:43][CH:42]=1)(=[O:40])=[O:39])([CH3:36])([CH3:35])[CH3:34].[F-].[K+].O>C1(C)C=CC=CC=1>[C:33]([NH:37][S:38]([C:41]1[S:45][C:44]([C:18]2[N:17]=[CH:16][N:15]([C:10]3[N:9]=[C:8]([C:5]4[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=4)[CH:13]=[C:12]([CH3:14])[N:11]=3)[CH:19]=2)=[N:43][CH:42]=1)(=[O:39])=[O:40])([CH3:36])([CH3:34])[CH3:35]
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참가 물질

6

반응물 4

HCID 962WaterHCID 522689Potassium FluorideHCID 434557712-Chloro-thiazole-5-sulfonic acid tert-butylamideHCID 574688274-(4-Chloro-phenyl)-6-methyl-2-(4-tributylstannanyl-imidazol-1-yl)-pyrimidine

생성물 1

HCID 57468959N-tert-butyl-2-{1-[4-(4-chloro-phenyl)-6-methyl-pyrimidin-2-yl]-1H-imidazol-4-yl}-thiazole-5-sulfonamide수율 25.6%

시약·촉매·용매 1

HCID 1140Toluene용매

실험 절차

A stirred mixture of 4-(4-chloro-phenyl)-6-methyl-2-(4-tributylstannanyl-imidazol-1-yl)-pyrimidine (Example G.3) (0.45 g, 0.80 mmol), 2-chloro-thiazole-5-sulfonic acid tert-butylamide (Example H.1) (0.225 g, 0.88 mmol), tetrakis(triphenyl-phosphine)palladium (0.056 g, 0.048 mmol) in toluene (10 mL) was heated under reflux conditions for 15 h. The mixture was poured into saturated potassium fluoride solution (10 mL), water (40 mL) was added and the water layer was extracted with ethyl acetate (2×60 mL). The combined organic layers were washed with brine (60 mL), dried (MgSO4) and evaporated. The crude product was purified by flash chromatography (heptane/ethyl acetate) and crystallization (THF/hexane) to yield N-tert-butyl-2-{1-[4-(4-chloro-phenyl)-6-methyl-pyrimidin-2-yl]-1H-imidazol-4-yl}-thiazole-5-sulfonamide (0.1 g) as a light brown solid.

후처리

  1. temperaturewas heated under reflux conditions for 15 h
  2. additionwas added
  3. extractionthe water layer was extracted with ethyl acetate (2×60 mL)
  4. washThe combined organic layers were washed with brine (60 mL)
  5. dry with materialdried (MgSO4)
  6. customevaporated
  7. customThe crude product was purified by flash chromatography (heptane/ethyl acetate) and crystallization (THF/hexane)

출처 및 근거

ORD 기록
ord-6affcc11cb9a4af6af97ee9c3d35471c
출처 데이터셋
uspto-grants-2012_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08183262B2

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