Hydrochloric Acid → HCID 58456314、化合物

HRID 410509

反応式

HRID 410509 の反応式
[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

参加物

10

反応物 6

HCID 313Hydrochloric AcidHCID 67803Tetramethylammonium fluorideHCID 552549(Trifluoromethyl)trimethylsilane3 回HCID 2724141Tetrabutylammonium FluorideHCID 23665647Potassium tert-butoxideHCID 58456406HCID 58456406、化合物

生成物 1

HCID 58456314HCID 58456314、化合物収率 67.6%

試薬・触媒・溶媒 3

HCID 2724141Tetrabutylammonium Fluoride触媒HCID 3283Diethyl Ether溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

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=+++

後処理

  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

出典と根拠

ORDレコード
ord-f0cd0ba6ea1c4c41ad1d56b54decad78
出典データセット
uspto-grants-2014_06
特許番号
US08759366B2

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