2-Aminothiazole → 3-cyclohexyl-2-(4-methanesulfonyl-phenyl)-N-thiazol-2-yl-propionamide

HRID 398616노트

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HRID 398616 반응식
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.BrN1C(=O)CCC1=O.[CH:28]1([CH2:34][CH:35]([C:39]2[CH:44]=[CH:43][C:42]([S:45]([CH3:48])(=[O:47])=[O:46])=[CH:41][CH:40]=2)[C:36]([OH:38])=O)[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1.[NH2:49][C:50]1[S:51][CH:52]=[CH:53][N:54]=1>C(Cl)Cl>[CH:28]1([CH2:34][CH:35]([C:39]2[CH:44]=[CH:43][C:42]([S:45]([CH3:48])(=[O:47])=[O:46])=[CH:41][CH:40]=2)[C:36]([NH:49][C:50]2[S:51][CH:52]=[CH:53][N:54]=2)=[O:38])[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33]1

참가 물질

6

반응물 4

HCID 21552-AminothiazoleHCID 11776TriphenylphosphineHCID 67184N-bromobutanimideHCID 223152003-Cyclohexyl-2-(4-methanesulfonyl-phenyl)-propionic acid

생성물 1

HCID 223152423-cyclohexyl-2-(4-methanesulfonyl-phenyl)-N-thiazol-2-yl-propionamide수율 92.3%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

반응 조건

온도
0 °C

실험 절차

A solution of triphenylphosphine (416 mg, 1.58 mmol) in methylene chloride (8 mL) was cooled to 0° C. and then treated with N-bromosuccinimide (281 mg, 1.58 mmol). The reaction mixture was stirred at 0° C. for 30 min and then treated with a solution of 3-cyclohexyl-2-(4-methanesulfonyl-phenyl)-propionic acid (290 mg, 0.93 mmol) in methylene chloride (5 mL). The clear solution was stirred for 15 min at 0° C. and then allowed to warm to 25° C. where it was stirred for 1.5 h. The reaction mixture was then treated with 2-aminothiazole (233 mg, 2.32 mmol), and the resulting suspension was stirred for 20 h at 25° C. The reaction mixture was concentrated in vacuo to remove methylene chloride, and the residue was diluted with ethyl acetate (50 mL) and a 1N aqueous hydrochloric acid solution (50 mL). The two layers were separated, and the aqueous layer was extracted with ethyl acetate (1×30 mL). The combined organic extracts were successively washed with a saturated aqueous sodium bicarbonate solution (1×50 mL) and a saturated aqueous sodium chloride solution (1×50 mL), dried over anhydrous magnesium sulfate, filtered, and, concentrated in vacuo. Biotage chromatography (FLASH 40S, Silica, 4/1 to 1/1 hexanes/ethyl acetate) afforded 3-cyclohexyl-2-(4-methanesulfonyl-phenyl)-N-thiazol-2-yl-propionamide (337 mg, 92%) as an amorphous solid: EI-HRMS m/e calcd for C19H24N2O3S2 (M+) 392.1228, found 392.1230.

후처리

  1. stirringThe clear solution was stirred for 15 min at 0° C.
  2. temperatureto warm to 25° C. where it
  3. stirringwas stirred for 1.5 h
  4. stirringthe resulting suspension was stirred for 20 h at 25° C
  5. concentrationThe reaction mixture was concentrated in vacuo
  6. customto remove methylene chloride
  7. additionthe residue was diluted with ethyl acetate (50 mL)
  8. customThe two layers were separated
  9. extractionthe aqueous layer was extracted with ethyl acetate (1×30 mL)
  10. washThe combined organic extracts were successively washed with a saturated aqueous sodium bicarbonate solution (1×50 mL)
  11. dry with materiala saturated aqueous sodium chloride solution (1×50 mL), dried over anhydrous magnesium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-aa4c85763d014806a09fe37e372c58a9
출처 데이터셋
uspto-grants-2003_08
특허 번호
US06610846B1

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