Sodium hydride → 3-(1-Benzyloxy-7-chloro-isoquinolin-6-yloxy)-cyclobutylamine

HRID 402540Notes

Reaction equation

HRID 402540 reaction equation
[H-].[Na+].[NH2:3][CH:4]1[CH2:7][CH:6]([OH:8])[CH2:5]1.[CH2:9]([O:16][C:17]1[C:26]2[C:21](=[CH:22][C:23](F)=[C:24]([Cl:27])[CH:25]=2)[CH:20]=[CH:19][N:18]=1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1>CC(N(C)C)=O>[CH2:9]([O:16][C:17]1[C:26]2[C:21](=[CH:22][C:23]([O:8][CH:6]3[CH2:7][CH:4]([NH2:3])[CH2:5]3)=[C:24]([Cl:27])[CH:25]=2)[CH:20]=[CH:19][N:18]=1)[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 457898893-aminocyclobutanol(SALTDATA: FREE)HCID 598182521-Benzyloxy-7-chloro-6-fluoro-isoquinoline

Product 1

HCID 592248403-(1-Benzyloxy-7-chloro-isoquinolin-6-yloxy)-cyclobutylamineYield 30.5%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent3×

Procedure

To a suspension of 459 mg (11.5 mmol) of sodium hydride (60%) in 16 mL of dimethyl acetamide was added a solution of 333 mg (3.82 mmol) of 3-amino-cyclobutanol (50) in 8 ml of dimethyl acetamide. After stirring for 60 min at room temperature a solution of 1.00 g (3.48 mmol) of 1-benzyloxy-7-chloro-6-fluoro-isoquinoline (11) in 16 ml of dimethyl acetamide was added and stirring was continued first at room temperature, then for 2 h at 50° C. until the reaction went to completion. The reaction was quenched by addition of water and the reaction mixture was extracted three times with a mixture of dichloromethane and 2-propanol (3:1). 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 377 mg of the title compound (51) as a mixture of diastereoisomers. Rt=0.85 min (Method H). Detected mass: 355.1 (M+H+).

Workup

  1. additionwas added
  2. customwas continued first at room temperature
  3. customThe reaction was quenched by addition of water
  4. extractionthe reaction mixture was extracted three times
  5. additionwith a mixture of dichloromethane and 2-propanol (3:1)
  6. customThe combined organic layers were evaporated
  7. additionwater was added
  8. customto remove remainders of dimethyl acetamide
  9. customThe obtained crude product
  10. customwas purified by silica gel chromatography

Sources & evidence

ORD record
ord-cbe20d510efc4c62b7042c4f977f36cd
Source dataset
uspto-grants-2014_06
Patent number
US08742116B2

Reaction notes

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