Sodium hydride → 4-[({4-[4-cyclopropyl-2-(2-trifluoromethoxy-phenyl)-2H-pyrazol-3-ylmethoxy]-2-methyl-phenyl}-methyl-amino)-methyl]-2-methoxy-benzoic acid methyl ester

HRID 2261869ノート

反応式

HRID 2261869 の反応式
[H-].[Na+].[CH:3]1([C:6]2[CH:10]=[N:9][N:8]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[O:17][C:18]([F:21])([F:20])[F:19])[C:7]=2[CH2:22][O:23][C:24]2[CH:29]=[CH:28][C:27]([NH:30][CH3:31])=[C:26]([CH3:32])[CH:25]=2)[CH2:5][CH2:4]1.[CH3:33][O:34][C:35](=[O:46])[C:36]1[CH:41]=[CH:40][C:39]([CH2:42]Br)=[CH:38][C:37]=1[O:44][CH3:45]>CN(C=O)C.O>[CH3:33][O:34][C:35](=[O:46])[C:36]1[CH:41]=[CH:40][C:39]([CH2:42][N:30]([C:27]2[CH:28]=[CH:29][C:24]([O:23][CH2:22][C:7]3[N:8]([C:11]4[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=4[O:17][C:18]([F:20])([F:21])[F:19])[N:9]=[CH:10][C:6]=3[CH:3]3[CH2:4][CH2:5]3)=[CH:25][C:26]=2[CH3:32])[CH3:31])=[CH:38][C:37]=1[O:44][CH3:45]

参加物

6

反応物 3

HCID 24758Sodium hydrideHCID 11288398Methyl 4-(bromomethyl)-2-methoxybenzoateHCID 57443372{4-[4-Cyclopropyl-2-(2-trifluoromethoxy-phenyl)-2H-pyrazol-3-ylmethoxy]-2-methyl-phenyl}-methyl-amine

生成物 1

HCID 675285424-[({4-[4-cyclopropyl-2-(2-trifluoromethoxy-phenyl)-2H-pyrazol-3-ylmethoxy]-2-methyl-phenyl}-methyl-amino)-methyl]-2-methoxy-benzoic acid methyl ester収率 68%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
40 °C

実験手順

Sodium hydride (60% in mineral oil, 30 mg, 0.75 mmol) is added to a solution of {4-[4-cyclopropyl-2-(2-trifluoromethoxy-phenyl)-2H-pyrazol-3-ylmethoxy]-2-methyl-phenyl}-methyl-amine (0.31 g, 0.75 mmol) and 4-bromomethyl-2-methoxy-benzoic acid methyl ester (0.320 g, 1.23 mmol) in DMF (3 mL) at room temperature. The reaction is heated to 40° C. for 2 h. The mixture is diluted with water and is extracted with ethyl acetate. The combined organic layers are washed with brine and dried over MgSO4. The crude residue is purified via radial chromatography (2 mm plate, 20 to 40 THF-heptane) to afford 4-[({4-[4-cyclopropyl-2-(2-trifluoromethoxy-phenyl)-2H-pyrazol-3-ylmethoxy]-2-methyl-phenyl}-methyl-amino)-methyl]-2-methoxy-benzoic acid methyl ester (303 mg, 68%). ES/MS m/e 596.0 (M+1).

後処理

  1. extractionis extracted with ethyl acetate
  2. washThe combined organic layers are washed with brine
  3. dry with materialdried over MgSO4
  4. customThe crude residue is purified via radial chromatography (2 mm plate, 20 to 40 THF-heptane)

出典と根拠

ORDレコード
ord-4f5488de012c4c929a05300be613ddee
出典データセット
uspto-grants-2010_12
特許番号
US07846960B2

反応ノート

読み込み中…