Water → 2-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-8-chloro-7-[(1,1,1-trifluoropropan-2-yl)oxy]-3,4-dihydroisoquinolin-1(2H)-one

HRID 577484ノート

反応式

HRID 577484 の反応式
[Cl:1][C:2]1[C:3]([O:13][CH:14]([CH3:19])[C:15]([F:18])([F:17])[F:16])=[CH:4][CH:5]=[C:6]2[C:11]=1[C:10](=[O:12])[NH:9][CH2:8][CH2:7]2.[H-].[Na+].[CH2:22]([O:29][C:30]1[C:35]([CH2:36]Cl)=[C:34]([CH3:38])[CH:33]=[C:32]([CH3:39])[N:31]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.O>CN(C=O)C>[CH2:22]([O:29][C:30]1[C:35]([CH2:36][N:9]2[CH2:8][CH2:7][C:6]3[C:11](=[C:2]([Cl:1])[C:3]([O:13][CH:14]([CH3:19])[C:15]([F:18])([F:16])[F:17])=[CH:4][CH:5]=3)[C:10]2=[O:12])=[C:34]([CH3:38])[CH:33]=[C:32]([CH3:39])[N:31]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

参加物

6

反応物 4

HCID 962WaterHCID 24758Sodium hydrideHCID 612578682-(Benzyloxy)-3-(chloromethyl)-4,6-dimethylpyridineHCID 867237098-chloro-7-[(1,1,1-trifluoropropan-2-yl)oxy]-3,4-dihydroisoquinolin-1(2H)-one

生成物 1

HCID 867237102-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-8-chloro-7-[(1,1,1-trifluoropropan-2-yl)oxy]-3,4-dihydroisoquinolin-1(2H)-one収率 80%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
0 °C

実験手順

To a solution of 8-chloro-7-[(1,1,1-trifluoropropan-2-yl)oxy]-3,4-dihydroisoquinolin-1(2H)-one (58a, 50 mg, 0.17 mmol) in dry DMF (6 mL) was added portionwise NaH (60% in oil, 21 mg, 0.51 mmol) at 0° C. under N2 atmosphere. The resulting mixture was stirred at 0° C. for 10 minutes and then 2-(benzyloxy)-3-(chloromethyl)-4,6-dimethylpyridine (Cpd Z, 76 mg, 0.29 mmol) was added. The resulting mixture was stirred at room temperature overnight. To the reaction mixture was added H2O (20 mL). The mixture was extracted with EtOAc (2×10 mL). The combined organic layers were washed with brine (4×15 mL), dried over Na2SO4 and concentrated under vacuum. The residue was purified by column chromatography (petroleum ether/EtOAc=6:1) to give 2-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-8-chloro-7-[(1,1,1-trifluoropropan-2-yl)oxy]-3,4-dihydroisoquinolin-1(2H)-one (58b, 70 mg, 80%) as a colorless oil.

後処理

  1. stirringThe resulting mixture was stirred at room temperature overnight
  2. extractionThe mixture was extracted with EtOAc (2×10 mL)
  3. washThe combined organic layers were washed with brine (4×15 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under vacuum
  6. customThe residue was purified by column chromatography (petroleum ether/EtOAc=6:1)

出典と根拠

ORDレコード
ord-bc6c127bc5bf4e6ba806434e63dbc524
出典データセット
uspto-grants-2015_05
特許番号
US09040515B2

反応ノート

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