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

HRID 604083
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HRID 604083 반응식
[F:1][C:2]([F:47])([F:46])[C:3]1[CH:4]=[C:5]([CH:39]=[C:40](C(F)(F)F)[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.[C:48]1(B(O)O)[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1.C(=O)([O-])[O-].[Cs+].[Cs+].O>O1CCOCC1.C(OCC)(=O)C>[F:1][C:2]([F:47])([F:46])[C:3]1[CH:4]=[C:5]([CH:39]=[C:40]([C:2]([F:47])([F:46])[F:1])[CH:41]=1)[CH2:6][N:7]([C:8]1[N:9]=[CH:10][C:11]([N:14]2[CH2:15][CH2:16][O:17][CH2:18][CH2:19]2)=[CH:12][N:13]=1)[CH2:20][C:21]1[CH:26]=[C:25]([C:27]([F:29])([F:28])[F:30])[CH:24]=[CH:23][C:22]=1[C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1
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HCID 962WaterHCID 10796Cesium carbonateHCID 66827Phenylboronic 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 86626838(3,5-Bis-trifluoromethyl-benzyl)-(5-morpholin-4-yl-pyrimidin-2-yl)-(4-trifluoromethyl-biphenyl-2-ylmethyl)-amine
수율 57.8%

시약·촉매·용매 2

HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

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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 (200 mg) is dissolved in 1,4-dioxane (3 ml), and thereto are added phenyl boronic acid (69 mg), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium dichloromethane complex (23 mg) and cesium carbonate (183 mg), and the mixture is stirred under nitrogen atmosphere at 80° C. for 1 day. The reaction solution is cooled to room temperature, and thereto are added water and ethyl acetate, and the mixture 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 NH-silica gel column chromatography (hexane:ethyl acetate=19:1→4:1) to give (3,5-bis-trifluoromethyl-benzyl)-(5-morpholin-4-yl-pyrimidin-2-yl)-(4-trifluoromethyl-biphenyl-2-ylmethyl)-amine (52 mg). MS (m/z): 641 [M+H]+

후처리

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

출처 및 근거

ORD 기록
ord-607db24bc78a4b81a4fa4840fdf980a9
출처 데이터셋
uspto-grants-2011_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07906517B2

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