Hydrochloric Acid → HCID 58456314, 화합물

HRID 410509

반응식

HRID 410509 반응식
[CH:1]1([C:4]([C:6]2[S:7][C:8]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([NH:17][C:18]4[N:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=[CH:20][N:19]=4)[CH:12]=3)=[CH:9][N:10]=2)=[O:5])[CH2:3][CH2:2]1.[F:28][C:29]([Si](C)(C)C)([F:31])[F:30].[F-].C[N+](C)(C)C.CC([O-])(C)C.[K+].CCCC[N+](CCCC)(CCCC)CCCC.[F-].Cl>O1CCCC1.CCCC[N+](CCCC)(CCCC)CCCC.[F-].CCOCC>[CH:1]1([C:4]([C:6]2[S:7][C:8]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([NH:17][C:18]4[N:23]=[C:22]([C:24]([F:25])([F:26])[F:27])[CH:21]=[CH:20][N:19]=4)[CH:12]=3)=[CH:9][N:10]=2)([OH:5])[C:29]([F:31])([F:30])[F:28])[CH2:3][CH2:2]1

참가 물질

10

반응물 6

HCID 313Hydrochloric AcidHCID 67803Tetramethylammonium fluorideHCID 552549(Trifluoromethyl)trimethylsilane3회HCID 2724141Tetrabutylammonium FluorideHCID 23665647Potassium tert-butoxideHCID 58456406HCID 58456406, 화합물

생성물 1

HCID 58456314HCID 58456314, 화합물수율 67.6%

시약·촉매·용매 3

HCID 2724141Tetrabutylammonium Fluoride촉매HCID 3283Diethyl Ether용매HCID 8028Tetrahydrofuran용매

실험 절차

TBAF (1 M, 3.71 μL, 3.71 μmol) was added to a stirred, cooled (0° C.) mixture of cyclopropyl[5-(3-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]methanone (29 mg, 0.074 mmol) and (trifluoromethyl)trimethylsilane (14.24 μL, 0.089 mmol) in tetrahydrofuran (0.2 mL) and the mixture was stirred at room temperature for 4 h. Additional TMSCF3 (20 μL) and tetramethyammonium fluoride (0.811 mg, 7.43 μmol) were added and the mixture was left to stir overnight. Additional TMSCF3 (22 μL) and KOtBu (1M in TIM, 74 μL) were added to the mixture and left to stir for 2 days. The mixture was treated with TBAF (74 μL), ether and HCl, and extracted with ethyl acetate. The combined organics were concentrated, and purified by flash chromatography to give 1-cyclopropyl-2,2,2-trifluoro-1-[5-(3-{[4-(trifluoromethyl)-pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]ethanol (23 mg, 0.050 mmol, 67.2% yield). APCI: [M+H]+ m/z 461.1. 1H NMR (400 MHz, CDCl3): δ 8.72 (d, J=4.9 Hz, 1H); 8.19 (s, 1H); 7.97 (s, 1H); 7.52 (d, J=8.3 Hz, 1H); 7.48-7.40 (m, 2H); 7.32 (d, J=7.8 Hz, 1H); 7.12 (d, J=4.9 Hz, 1H); 4.53 (s, 1H); 1.58-1.51 (m, 1H); 1.01-0.94 (m, 1H); 0.77-0.67 (m, 1H); 0.59-0.51 (m, 2H). rhSYK activity=+++

후처리

  1. temperaturecooled
  2. waitthe mixture was left
  3. stirringto stir overnight
  4. waitleft
  5. stirringto stir for 2 days
  6. extractionextracted with ethyl acetate
  7. concentrationThe combined organics were concentrated
  8. custompurified by flash chromatography

출처 및 근거

ORD 기록
ord-f0cd0ba6ea1c4c41ad1d56b54decad78
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08759366B2

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