Water → (2'-Benzyloxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-(3,5-bis-trifluoromethyl-benzyl)-(5-morpholin-4-yl-pyrimidin-2-yl)-amine

HRID 604114

반응식

HRID 604114 반응식
[F:1][C:2]([F:47])([F:46])[C:3]1[CH:4]=[C:5]([CH:39]=[C:40]([C:42]([F:45])([F:44])[F:43])[CH:41]=1)[CH2:6][N:7]([CH2:20][C:21]1[CH:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[CH:23][C:22]=1OS(C(F)(F)F)(=O)=O)[C:8]1[N:13]=[CH:12][C:11]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)=[CH:10][N:9]=1.[CH2:48]([O:55][C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][C:57]=1B(O)O)[C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1.C(=O)([O-])[O-].[Cs+].[Cs+].O>O1CCOCC1.C(OCC)(=O)C>[CH2:48]([O:55][C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][C:57]=1[C:22]1[CH:23]=[CH:24][C:25]([C:27]([F:30])([F:29])[F:28])=[CH:26][C:21]=1[CH2:20][N:7]([CH2:6][C:5]1[CH:39]=[C:40]([C:42]([F:43])([F:44])[F:45])[CH:41]=[C:3]([C:2]([F:47])([F:1])[F:46])[CH:4]=1)[C:8]1[N:13]=[CH:12][C:11]([N:14]2[CH2:15][CH2:16][O:17][CH2:18][CH2:19]2)=[CH:10][N:9]=1)[C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1

참가 물질

7

반응물 4

HCID 962WaterHCID 10796Cesium carbonateHCID 2773253(2-(Benzyloxy)phenyl)boronic acidHCID 86626837Trifluoromethanesulfonic acid 2-{[(3,5-bis-trifluoromethyl-benzyl)-(5-morpholin-4-yl-pyrimidin-2-yl)-amino]-methyl}-4-trifluoromethyl-phenyl ester

생성물 1

HCID 86626864(2'-Benzyloxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-(3,5-bis-trifluoromethyl-benzyl)-(5-morpholin-4-yl-pyrimidin-2-yl)-amine수율 95%

시약·촉매·용매 2

HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

반응 조건

온도
80 °C

실험 절차

Trifluoromethanesulfonic acid 2-{[(3,5-bis-trifluoromethyl-benzyl)-(5-morpholin-4-yl-pyrimidin-2-yl)-amino]-methyl}-4-trifluoromethyl-phenyl ester (620 mg) is dissolved in 1,4-dioxane (10 ml) and thereto are added 2-benzyloxyphenyl boronic acid (398 mg), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium dichloromethane complex (142 mg) and cesium carbonate (567 mg), and the mixture is stirred under nitrogen atmosphere at 80° C. overnight. The reaction solution is cooled to room temperature, and thereto are added water and ethyl acetate, and the insoluble materials are removed by filtration through Celite™. The filtrate is separated, and the organic layer is washed with a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is purified by silica gel column chromatography (hexane:ethyl acetate=19:1→4:1) to give (2′-benzyloxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-(3,5-bis-trifluoromethyl-benzyl)-(5-morpholin-4-yl-pyrimidin-2-yl)-amine (617 mg). MS (m/z): 747 [M+H]+

후처리

  1. temperatureThe reaction solution is cooled to room temperature
  2. customthe insoluble materials are removed by filtration through Celite™
  3. customThe filtrate is separated
  4. washthe organic layer is washed with a saturated brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue is purified by silica gel column chromatography (hexane:ethyl acetate=19:1→4:1)

출처 및 근거

ORD 기록
ord-add5d833908a4720a0cbe26d56e4e40b
출처 데이터셋
uspto-grants-2011_03
특허 번호
US07906517B2

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