Sodium hydride → 6-(4-Allyl-4-amino-cyclohexyl oxy)-7-chloro-2-(4-methoxy-benzyl)-2H-isoquinolin-1-one

HRID 2370272Notes

Reaction equation

HRID 2370272 reaction equation
[H-].[Na+].[CH2:3]([C:6]1([NH2:13])[CH2:11][CH2:10][CH:9]([OH:12])[CH2:8][CH2:7]1)[CH:4]=[CH2:5].[Cl:14][C:15]1[CH:24]=[C:23]2[C:18]([CH:19]=[CH:20][N:21]([CH2:26][C:27]3[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=3)[C:22]2=[O:25])=[CH:17][C:16]=1F>CC(N(C)C)=O>[CH2:3]([C:6]1([NH2:13])[CH2:11][CH2:10][CH:9]([O:12][C:16]2[CH:17]=[C:18]3[C:23](=[CH:24][C:15]=2[Cl:14])[C:22](=[O:25])[N:21]([CH2:26][C:27]2[CH:28]=[CH:29][C:30]([O:33][CH3:34])=[CH:31][CH:32]=2)[CH:20]=[CH:19]3)[CH2:8][CH2:7]1)[CH:4]=[CH2:5]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 592260294-Allyl-4-amino-cyclohexanolHCID 598182477-Chloro-6-fluoro-2-[(4-methoxyphenyl)methyl]isoquinolin-1(2H)-one

Product 1

HCID 592260516-(4-Allyl-4-amino-cyclohexyl oxy)-7-chloro-2-(4-methoxy-benzyl)-2H-isoquinolin-1-oneYield 25.3%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent3×

Procedure

155 mg (3.86 mmol) of sodium hydride (60%) were suspended in 3 mL of dimethyl acetamide and 220 mg (1.42 mmol) of 4-allyl-4-amino-cyclohexanol (16), dissolved in 1 mL of dimethyl acetamide, were added dropwise. After 1 h, 409 mg (1.29 mmol) of 2-(4-methoxy-benzyl)-6-fluoro-7-chloro-2H-isoquinolin-1-one (10), dissolved in another 2 mL of dimethyl acetamide, were added. The reaction mixture was stirred at room temperature until the reaction was complete. The mixture was quenched by dropwise addition of water, extracted with a mixture of dichloromethane and 2-propanol (3:1) and the combined organic layers were evaporated. Water was added and the crude product was subjected to lyophilization to remove remainders of dimethyl acetamide. The obtained crude product was purified by silica gel chromatography to yield 148 mg of the title compound (17) as diastereomeric mixture. Rt=1.35 min, 1.40 min (Method B). Detected mass: 453.3 (M+H+).

Workup

  1. additionwere added dropwise
  2. additionwere added
  3. customThe mixture was quenched by dropwise addition of water
  4. extractionextracted with a mixture of dichloromethane and 2-propanol (3:1)
  5. customthe combined organic layers were evaporated
  6. additionWater was added
  7. customto remove remainders of dimethyl acetamide
  8. customThe obtained crude product
  9. customwas purified by silica gel chromatography

Sources & evidence

ORD record
ord-ca12d1bdfc804e0f9241564ee7652738
Source dataset
uspto-grants-2014_04
Patent number
US08710077B2

Reaction notes

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