Trifluoroacetic acid → HCID 24782989, compound

HRID 1366763Notes

Reaction equation

HRID 1366763 reaction equation
C(OC([CH:8]([NH2:19])[C@H:9]1[CH2:13][CH2:12][C@@H:11]([O:14]S(C)(=O)=O)[CH2:10]1)=O)(C)(C)C.O[C:21]1[CH:22]=[C:23]2[C:28](=[CH:29][CH:30]=1)[C:27](=[O:31])[NH:26][CH:25]=[CH:24]2.C(=O)([O-])[O-].[K+].[K+].C([O-])(O)=O.[Na+].FC(F)(F)C(O)=O>CN(C)C=O.CO.ClCCl>[NH2:19][CH2:8][C@H:9]1[CH2:13][CH2:12][C@@H:11]([O:14][C:21]2[CH:22]=[C:23]3[C:28](=[CH:29][CH:30]=2)[C:27](=[O:31])[NH:26][CH:25]=[CH:24]3)[CH2:10]1

Participants

9

Reactant 5

HCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 516892Sodium BicarbonateHCID 105111706-hydroxyisoquinolin-1(2H)-oneHCID 86618629HCID 86618629, compound

Product 1

HCID 24782989HCID 24782989, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
90 °C

Procedure

A solution of the methanesulfonic acid (1R,3S)-3-(tert-butoxycarbonyl-aminomethyl)cyclopentyl ester in N,N-dimethylformamide (2 ml) was added over 15 minutes to a stirred solution of 6-hydroxy-2H-isoquinolin-1-one (161 mg, 1 mmol) and potassium carbonate (276 mg) in N, N-dimethylformamide (2 ml) at 100° C. The mixture was stirred at 90° C. for 4 h then allowed to cool to ambient temperature and stirred overnight. Saturated aqueous NaHCO3 was added, the mixture was extracted with chloroform: isopropanol (3:1) and the organic phase concentrated in vacuo to give a residue. A dichloromethane: trifluoroacetic acid solution (3:1, 3 ml) was added to the residue and the resultant mixture stirred for 3.5 h, then concentrated in vacuo to give a residue. The residue was loaded onto a pre-acidified SCX column using methanol and eluted with 2M ammonia in methanol to afford crude (1R,3S)-6-(3-aminomethylcyclopentyloxy)-2H-isoquinolin-1-one, which was purified by prep-HPLC (2 mg); EI-MS: m/z=259.1 [M+H]+.

Workup

  1. temperatureto cool to ambient temperature
  2. stirringstirred overnight
  3. extractionthe mixture was extracted with chloroform: isopropanol (3:1)
  4. concentrationthe organic phase concentrated in vacuo
  5. customto give a residue
  6. concentrationconcentrated in vacuo
  7. customto give a residue
  8. washeluted with 2M ammonia in methanol

Sources & evidence

ORD record
ord-39a9d3f952fe4e9cb9700b924cf8e5c0
Source dataset
uspto-grants-2011_02
Patent number
US07893088B2

Reaction notes

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