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 1175897ノート

反応式

HRID 1175897 の反応式
[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

参加物

8

反応物 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

生成物 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)benzamide収率 31.8%

試薬・触媒・溶媒 3

HCID 11251615Bromotris(triphenylphosphine)copper(I)触媒HCID 962Water溶媒HCID 31374Dimethylacetamide溶媒

反応条件

温度
160 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-8d46b0d71ff84e66a8ddd247055924b5
出典データセット
uspto-grants-2010_11
特許番号
US07842694B2

反応ノート

読み込み中…