Acetic Acid → HCID 178511695, compound

HRID 1913121Notes

Reaction equation

HRID 1913121 reaction equation
Cl.[NH2:2][C@@H:3]1[CH2:8][CH2:7][C@H:6]([O:9][C:10]2[CH:11]=[C:12]3[C:17](=[CH:18][C:19]=2Cl)[C:16]([OH:21])=[N:15][CH:14]=[CH:13]3)[CH2:5][CH2:4]1.C(N(CC)CC)C.C(O)(=O)C.C([BH3-])#N.[Na+]>CO>[NH2:2][C@@H:3]1[CH2:4][CH2:5][C@H:6]([O:9][C:10]2[CH:11]=[C:12]3[C:17](=[CH:18][CH:19]=2)[C:16](=[O:21])[NH:15][CH:14]=[CH:13]3)[CH2:7][CH2:8]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 8471TriethylamineHCID 5003444Sodium cyanoborohydrideHCID 178479273HCID 178479273, compound

Product 1

HCID 178511695HCID 178511695, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

150 mg (0.46 mmol) of 6-cis-(4-amino-cyclohexyloxy)-7-chloro-2H-isoquinolin-1-one hydrochloride (10) were dissolved in 10 ml of methanol. After addition of molecular sieves 4 A, 92.3 mg (0.57 mmol) of triethyl amine, 273.8 mg (4.56 mmol) of acetic acid and 0.57 mmol of the corresponding aldehyde, a solution of 86.0 mg (1.37 mmol) of sodium cyanoboro hydride is added dropwise and the mixture is stirred at room temperature until complete conversion is achieved. In some cases it was necessary to heat the mixture to 70° C. to achieve complete conversion. For the isolation of the products the solution was filtered and the solvent was removed under reduced pressure. The residue was dissolved in dichloromethane, washed with 1 N NaOH and sat. sodium chloride solution, dried with magnesium sulfate and evaporated. The mono- or bis alkylated products, if obtained, were purified by preparative HPLC or precipitated from methanolic HCl

Workup

  1. temperatureto heat the mixture to 70° C.
  2. filtrationFor the isolation of the products the solution was filtered
  3. customthe solvent was removed under reduced pressure
  4. dissolutionThe residue was dissolved in dichloromethane
  5. washwashed with 1 N NaOH and sat. sodium chloride solution
  6. dry with materialdried with magnesium sulfate
  7. customevaporated
  8. customif obtained
  9. customwere purified by preparative HPLC
  10. customprecipitated from methanolic HCl

Sources & evidence

ORD record
ord-117c25d6cf0c4ff0b58453d12c1d7a20
Source dataset
uspto-grants-2013_12
Patent number
US08609691B2

Reaction notes

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