Acetic Acid → 7-Chloro-6-(1-isopropyl-piperidin-4-yloxy)-2H-isoquinolin-1-one

HRID 1930215Notes

Reaction equation

HRID 1930215 reaction equation
Cl.[Cl:2][C:3]1[CH:12]=[C:11]2[C:6]([CH:7]=[CH:8][NH:9][C:10]2=[O:13])=[CH:5][C:4]=1[O:14][CH:15]1[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1.C(N(CC)CC)C.C(O)(=O)C.[CH3:32][C:33]([CH3:35])=O.C([BH3-])#N.[Na+]>CO>[Cl:2][C:3]1[CH:12]=[C:11]2[C:6]([CH:7]=[CH:8][NH:9][C:10]2=[O:13])=[CH:5][C:4]=1[O:14][CH:15]1[CH2:20][CH2:19][N:18]([CH:33]([CH3:35])[CH3:32])[CH2:17][CH2:16]1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 180Acetone2×HCID 8471TriethylamineHCID 5003444Sodium cyanoborohydride2×HCID 674580427-Chloro-6-(piperidin-4-yloxy)-2h-isoquinolin-1-one-hydro-chloride

Product 1

HCID 576524997-Chloro-6-(1-isopropyl-piperidin-4-yloxy)-2H-isoquinolin-1-oneYield 17.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

64 mg (0.23 mmol) of 7-chloro-6-(piperidin-4-yloxy)-2H-isoquinolin-1-one-hydro-chloride (54) were dissolved in 5 mL of methanol. 41.4 mg (0.41 mmol) of triethyl amine were added and the mixture stirred at room temperature for 10 minutes. After adding freshly dried molecular sieves, 122.4 mg (2.04 mmol) acetic acid, 26.7 mg (0.46 mmol) of acetone and 43.3 mg (0.69 mmol) of sodium cyanoborohydride, the reaction mixture was refluxed for 8 h. After the addition of 2 equivalents acetone and 2 equivalents of sodium cyanoborohydride at room temperature, the reaction was refluxed for another 2 h to complete conversion. For working up, the mixture was filtered and the filtrate was evaporated. The residue was dissolved in dichloromethane, washed twice with 2 N NaOH and water and dried over MgSO4. After evaporation of the solvent and purification by preparative HPLC, 13 mg of the title compound were obtained as trifluoroacetate. Rt=0.96 min (Method B). Detected mass: 321.1/323.2 (M+H+).

Workup

  1. temperaturethe reaction mixture was refluxed for 8 h
  2. temperaturethe reaction was refluxed for another 2 h
  3. filtrationthe mixture was filtered
  4. customthe filtrate was evaporated
  5. dissolutionThe residue was dissolved in dichloromethane
  6. washwashed twice with 2 N NaOH and water
  7. dry with materialdried over MgSO4
  8. customAfter evaporation of the solvent and purification by preparative HPLC

Sources & evidence

ORD record
ord-e4feee1783b7402e9b1a5deba1085ff7
Source dataset
uspto-grants-2012_05
Patent number
US08188117B2

Reaction notes

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