Sodium hydride → 1-[(1S,2S,4S)-5-(7-Chloro-1-methoxy-isoquinolin-6-yloxy)-2-phenyl-bicyclo[2.2.1]hept-2-yl]-propylamine

HRID 45192Notes

Reaction equation

HRID 45192 reaction equation
[NH2:1][CH:2]([C@@:5]1([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:10][C@@H:9]2[CH2:11][C@H:6]1[CH2:7][CH:8]2[OH:12])[CH2:3][CH3:4].[H-].[Na+].[Cl:21][C:22]1[CH:31]=[C:30]2[C:25]([CH:26]=[CH:27][N:28]=[C:29]2[O:32][CH3:33])=[CH:24][C:23]=1F.C([O-])(O)=O.[Na+]>CC(N(C)C)=O>[Cl:21][C:22]1[CH:31]=[C:30]2[C:25]([CH:26]=[CH:27][N:28]=[C:29]2[O:32][CH3:33])=[CH:24][C:23]=1[O:12][CH:8]1[CH2:7][C@@H:6]2[CH2:11][C@H:9]1[CH2:10][C@@:5]2([CH:2]([NH2:1])[CH2:3][CH3:4])[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 583808287-Chloro-6-fluoro-1-methoxyisoquinolineHCID 58381039(1S,4S,5S)-5-(1-Amino-propyl)-5-phenyl-bicyclo[2.2.1]heptan-2-ol

Product 1

HCID 583809411-[(1S,2S,4S)-5-(7-Chloro-1-methoxy-isoquinolin-6-yloxy)-2-phenyl-bicyclo[2.2.1]hept-2-yl]-propylamineYield 9.5%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

200 mg (0.82 mmol) of (1S,4S,5S)-5-(1-Amino-propyl)-5-phenyl-bicyclo[2.2.1]heptan-2-ol (89) were dissolved in 5 mL anhydrous dimethylacetamide. Afterwards, 39 mg (1.63 mmol) of NaH were added, followed by the addition of 173 mg (0.82 mmol) of 7-chloro-6-fluoro-1-methoxy-isoquinoline (10). The mixture was stirred at ambient temperature for 20 h. Afterwards, 50 mL of a saturated aqueous NaHCO3-solution were added and the mixture extracted three times using 30 mL ethyl acetate each. The organic layer was dried using MgSO4 and evaporated. The residue was purified using chromatography on reversed phase (acetonitrile/water). The product-containing fractions were evaporated to half of the original volume, 10 mL of a saturated aqueous Na2CO3-solution was added and the mixture extracted three times using 20 mL of ethyl acetate each. The organic layer was dried using MgSO4, filtered and evaporated yielding 34 mg of the desired product 90. Rt=0.86 min (Method 18). Detected mass: 437.3 (M+H+)

Workup

  1. extractionthe mixture extracted three times
  2. customThe organic layer was dried
  3. customevaporated
  4. customThe residue was purified
  5. customThe product-containing fractions were evaporated to half of the original volume, 10 mL of a saturated aqueous Na2CO3-solution
  6. additionwas added
  7. extractionthe mixture extracted three times
  8. customThe organic layer was dried
  9. filtrationfiltered
  10. customevaporated

Sources & evidence

ORD record
ord-002f8121152d46c096a9eacbd3a825ca
Source dataset
uspto-grants-2013_09
Patent number
US08541449B2

Reaction notes

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