Water → 2-(4-Methoxy-benzyl)-6-((1S,3S)-3-amino-cyclopentyloxy)-2H-isoquinolin-1-one

HRID 402535Notes

Reaction equation

HRID 402535 reaction equation
[H-].[Na+].[NH2:3][C@H:4]1[CH2:8][CH2:7][C@H:6]([OH:9])[CH2:5]1.F[C:11]1[CH:12]=[C:13]2[C:18](=[CH:19][CH:20]=1)[C:17](=[O:21])[N:16]([CH2:22][C:23]1[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=1)[CH:15]=[CH:14]2.O>CC(N(C)C)=O>[CH3:30][O:29][C:26]1[CH:25]=[CH:24][C:23]([CH2:22][N:16]2[CH:15]=[CH:14][C:13]3[C:18](=[CH:19][CH:20]=[C:11]([O:9][C@H:6]4[CH2:7][CH2:8][C@H:4]([NH2:3])[CH2:5]4)[CH:12]=3)[C:17]2=[O:21])=[CH:28][CH:27]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 42614395(1S,3S)-3-Aminocyclopentan-1-olHCID 598182606-Fluoro-2-[(4-methoxyphenyl)methyl]isoquinolin-1-one

Product 1

HCID 592248392-(4-Methoxy-benzyl)-6-((1S,3S)-3-amino-cyclopentyloxy)-2H-isoquinolin-1-oneYield 49%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent3×

Conditions

Temperature
80 °C

Procedure

106 mg (4.20 mmol) of sodium hydride (95%) were suspended in 3 mL of dimethyl acetamide and 193 mg (1.40 mmol) of (1S,3S)-3-amino-cyclopentanol (34), dissolved in 1 mL of dimethyl acetamide, were added dropwise. After 1 h, 402 mg (1.42 mmol) of 2-(4-methoxy-benzyl)-6-fluoro-2H-isoquinolin-1-one (9), dissolved in another 3 mL of dimethyl acetamide, were added. The reaction mixture was stirred at 80° C. until the reaction was complete. The mixture was poured into water, extracted three times 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 250 mg of the title compound (39). Rt=1.20 min (Method E). Detected mass: 365.2 (M+H+).

Workup

  1. additionwere added dropwise
  2. additionwere added
  3. extractionextracted three times
  4. additionwith 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-781560f9d9294b6b808b054dca68a86f
Source dataset
uspto-grants-2014_06
Patent number
US08742116B2

Reaction notes

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