Toluene → 2-(difluoro(3-fluorophenoxy)methyl)-3-(3-fluoro-4-morpholinophenyl)-6-methyl-pyrimidin-4(3H)-one
反応式
[F:1][C:2]1[CH:3]=[C:4]([NH:14][C:15](=[O:20])[CH2:16][C:17](=O)[CH3:18])[CH:5]=[CH:6][C:7]=1[N:8]1[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1.[F:21][C:22]([F:34])([O:26][C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([F:33])[CH:28]=1)[C:23]([NH2:25])=O.C1(C)C=CC=CC=1.[NH4+].[Cl-]>C1(C)C(C)=CC=CC=1.C([O-])(C)C.C([O-])(C)C.C([O-])(C)C.C([O-])(C)C.[Ti+4]>[F:34][C:22]([F:21])([O:26][C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([F:33])[CH:28]=1)[C:23]1[N:14]([C:4]2[CH:5]=[CH:6][C:7]([N:8]3[CH2:13][CH2:12][O:11][CH2:10][CH2:9]3)=[C:2]([F:1])[CH:3]=2)[C:15](=[O:20])[CH:16]=[C:17]([CH3:18])[N:25]=1参加物
反応物 4
生成物 1
試薬・触媒・溶媒 2
反応条件
- 温度
- 165 °C
実験手順
A mixture of N-(3-fluoro-4-morpholinophenyl)-3-oxobutanamide (0.60 g, 2.14 mmol), 2,2-difluoro-2-(3-fluorophenoxy)acetamide (0.88 g, 4.29 mmol) and titanium tetraisopropanolate (4.87 g, 17.1 mmol) in xylene (20 mL) was stirred at 165° C. for 24 h. The mixture was cooled to rt and 60 mL of toluene and 80 mL of saturated NH4Cl aqueous solution were added. The resulting mixture was stirred at rt overnight and filtered and the filtrate was extracted with DCM (150 mL×3). The combined organic layers were dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=1:1) to give the title compound as a yellow solid (0.38 g, 40%). The compound was characterized by the following spectroscopic data:
後処理
- temperatureThe mixture was cooled to rt
- stirringThe resulting mixture was stirred at rt overnight
- filtrationfiltered
- extractionthe filtrate was extracted with DCM (150 mL×3)
- dry with materialThe combined organic layers were dried over anhydrous Na2SO4
- concentrationconcentrated in vacuo
- customThe residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=1:1)
出典と根拠
- ORDレコード
- ord-15ae61c5b24a4e61bf8b2381320619c2
- 出典データセット
- uspto-grants-2016_09
- 特許番号
- US09434695B2
反応ノート
読み込み中…