Ethyl Acetate → 3-{[6-(azetidin-1-ylcarbonyl)pyridin-3-yl]oxy}-5-({(1S)-2-[(difluoromethyl)oxy]-1-methylethyl}oxy)-N-(1-methyl-1H-pyrazol-3-yl)benzamide

HRID 1011726노트

반응식

HRID 1011726 반응식
[F:1][CH:2]([F:24])[O:3][CH2:4][C@@H:5]([O:7][C:8]1[CH:9]=[C:10]([CH:20]=[C:21]([OH:23])[CH:22]=1)[C:11]([NH:13][C:14]1[CH:18]=[CH:17][N:16]([CH3:19])[N:15]=1)=[O:12])[CH3:6].[N:25]1([C:29]([C:31]2[CH:36]=[CH:35][C:34](Br)=[CH:33][N:32]=2)=[O:30])[CH2:28][CH2:27][CH2:26]1.C(=O)([O-])[O-].[Cs+].[Cs+].C(OCC)(=O)C>CC(N(C)C)=O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]Br.O>[N:25]1([C:29]([C:31]2[N:32]=[CH:33][C:34]([O:23][C:21]3[CH:20]=[C:10]([CH:9]=[C:8]([O:7][C@@H:5]([CH3:6])[CH2:4][O:3][CH:2]([F:1])[F:24])[CH:22]=3)[C:11]([NH:13][C:14]3[CH:18]=[CH:17][N:16]([CH3:19])[N:15]=3)=[O:12])=[CH:35][CH:36]=2)=[O:30])[CH2:28][CH2:27][CH2:26]1

참가 물질

8

반응물 4

HCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 536296172-(Azetidin-1-ylcarbonyl)-5-bromopyridineHCID 591271223-[(2S)-1-(difluoromethoxy)propan-2-yl]oxy-5-hydroxy-N-(1-methylpyrazol-3-yl)benzamide

생성물 1

HCID 160396483-{[6-(azetidin-1-ylcarbonyl)pyridin-3-yl]oxy}-5-({(1S)-2-[(difluoromethyl)oxy]-1-methylethyl}oxy)-N-(1-methyl-1H-pyrazol-3-yl)benzamide수율 31.8%

시약·촉매·용매 3

HCID 11251615Bromotris(triphenylphosphine)copper(I)촉매HCID 962Water용매HCID 31374Dimethylacetamide용매

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온도
160 °C

실험 절차

A mixture of 3-({(1S)-2-[(difluoromethyl)oxy]-1-methylethyl}oxy)-5-hydroxy-N-(1-methyl-1H-pyrazol-3-yl)benzamide (220 mg, 0.64 mmol), 2-(azetidin-1-ylcarbonyl)-5-bromopyridine (171 mg, 0.71 mmol), cesium carbonate (419 mg, 1.29 mmol) and bromotris(triphenylphosphine)copper(I) (300 mg, 0.32 mmol) in DMA (5 mL) was stirred in a ‘Biotage initiator Microwave’ at 160° C. for 4 hours. The reaction mixture was added to ethyl acetate (50 mL) and water (50 mL), the organic layer washed with brine (50 mL), dried (MgSO4), filtered and the solvent removed in vacuo to give a brown oil. The residue was chromatographed on silica, eluting with 0-100% ethyl acetate in isohexane, to give the desired compound (102 mg).

후처리

  1. washthe organic layer washed with brine (50 mL)
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. customthe solvent removed in vacuo
  5. customto give a brown oil
  6. customThe residue was chromatographed on silica
  7. washeluting with 0-100% ethyl acetate in isohexane

출처 및 근거

ORD 기록
ord-d382df65b9eb4a6cbeaf047a25aa2f51
출처 데이터셋
uspto-grants-2011_07
특허 번호
US07977328B2

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