2-[5-(3-Ethynyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]propan-2-ol → 2-[5-(3-Ethyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]propan-2-ol

HRID 410545노트

반응식

HRID 410545 반응식
[C:1]([C:3]1[CH:4]=[C:5]([C:20]2[S:24][C:23]([C:25]([OH:28])([CH3:27])[CH3:26])=[N:22][CH:21]=2)[CH:6]=[C:7]([NH:9][C:10]2[N:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[CH:12][N:11]=2)[CH:8]=1)#[CH:2]>C(OCC)(=O)C.[Pd]>[CH2:1]([C:3]1[CH:4]=[C:5]([C:20]2[S:24][C:23]([C:25]([OH:28])([CH3:27])[CH3:26])=[N:22][CH:21]=2)[CH:6]=[C:7]([NH:9][C:10]2[N:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[CH:12][N:11]=2)[CH:8]=1)[CH3:2]

참가 물질

4

반응물 1

HCID 584563602-[5-(3-Ethynyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]propan-2-ol

생성물 1

HCID 584562962-[5-(3-Ethyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]propan-2-ol수율 63%

시약·촉매·용매 2

HCID 23938Palladium촉매HCID 8857Ethyl Acetate용매

실험 절차

To a solution of 2-[5-(3-ethynyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]propan-2-ol (19 mg, 0.047 mmol) in ethyl acetate (1 mL) was added Pd/C (10 wt %, 10.0 mg, 9.4 μmol, and the reaction vessel was then purged with H2 and stirred under an atmosphere of H2 (balloon) overnight. The catalyst was deactivated by addition of dichloromethane, then the mixture was filtered through Celite (ethyl acetate rinse) and concentrated in vacuo. The residue was then purified by preparative HPLC (50-90% CH3CN in 15 mM NH4HCO3(aq)) which provided 12 mg (0.029 mmol, 63%) of 2-[5-(3-ethyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]propan-2-ol as a white solid. MS ESI: [M+H]+ m/z 409.1. 1H NMR (400 MHz, (CD3)2CO): δ 9.20 (s, 1H); 8.82 (d, J=4.9 Hz, 1H); 8.12 (s, 1H); 7.94 (s, 1H); 7.67 (s, 1H); 7.25-7.20 (m, 2H); 5.02 (s, 1H); 2.70 (q, J=7.6 Hz, 2H); 1.63 (s, 6H); 1.28 (t, J=7.6 Hz, 3H). rhSYK activity=+++

후처리

  1. customthe reaction vessel was then purged with H2
  2. additionThe catalyst was deactivated by addition of dichloromethane
  3. filtrationthe mixture was filtered through Celite (ethyl acetate rinse)
  4. concentrationconcentrated in vacuo
  5. customThe residue was then purified by preparative HPLC (50-90% CH3CN in 15 mM NH4HCO3(aq)) which

출처 및 근거

ORD 기록
ord-e07dd0a9441346f5895ad8d38c420c72
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08759366B2

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