Sodium hydride → HCID 178454056, compound

HRID 2370725Notes

Reaction equation

HRID 2370725 reaction equation
[C:1]([O:5][C:6](=[O:15])[NH:7][C@H:8]1[CH2:13][CH2:12][C@H:11]([OH:14])[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[Cl:18][C:19]1[CH:28]=[C:27]2[C:22]([CH:23]=[CH:24][N:25]=[CH:26]2)=[CH:21][C:20]=1F>CN(C)C(=O)C>[C:1]([O:5][C:6](=[O:15])[NH:7][C@H:8]1[CH2:9][CH2:10][C@H:11]([O:14][C:20]2[CH:21]=[C:22]3[C:27](=[CH:28][C:19]=2[Cl:18])[CH:26]=[N:25][CH:24]=[CH:23]3)[CH2:12][CH2:13]1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 534189227-Chloro-6-fluoroisoquinolineHCID 178418329HCID 178418329, compound

Product 1

HCID 178454056HCID 178454056, compound

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

450 mg (0.21 mmol) trans-(4-Hydroxy-cyclohexyl)-carbamic acid tert-butyl ester were dissolved in 25 ml N,N-dimethyl acetamide. Under an argon atmosphere, 101 mg (4.2 mmol) sodium hydride were added and the mixture was stirred at room temperature. After 30 minutes, 250 mg (0.14 mmol) 7-chloro-6-fluoro-isoquinoline (6) were added and the solution was heated to 80° C. After 4 h, the solvent was removed under reduced pressure. The residue was taken up in H2O and extracted three times with ethyl acetate. The combined organic layers were dried over MgSO4 and evaporated. The crude product was purified by preparative HPLC, which delivered 18 mg of the title compound. Rt=1.38 min (Method #1). Detected mass: 377.2/379.3 (M+H+).

Workup

  1. temperaturethe solution was heated to 80° C
  2. waitAfter 4 h
  3. customthe solvent was removed under reduced pressure
  4. extractionextracted three times with ethyl acetate
  5. dry with materialThe combined organic layers were dried over MgSO4
  6. customevaporated
  7. customThe crude product was purified by preparative HPLC, which

Sources & evidence

ORD record
ord-f8a551ea041449c0985e074facdb9c0d
Source dataset
uspto-grants-2014_04
Patent number
US08710228B2

Reaction notes

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