Acetic Acid → HCID 16222359, compound

HRID 1435998Notes

Reaction equation

HRID 1435998 reaction equation
ClCCl.C(O)(=O)C.C(OC([N:15]1[CH2:20][CH2:19][CH:18]([S:21][C:22]2[CH:23]=[C:24]3[C:29](=[CH:30][CH:31]=2)[C:28](=[O:32])[NH:27][CH:26]=[CH:25]3)[CH2:17][CH2:16]1)=O)(C)(C)C>CO>[NH:15]1[CH2:16][CH2:17][CH:18]([S:21][C:22]2[CH:23]=[C:24]3[C:29](=[CH:30][CH:31]=2)[C:28](=[O:32])[NH:27][CH:26]=[CH:25]3)[CH2:19][CH2:20]1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 6344DichloromethaneHCID 68877258HCID 68877258, compound

Product 1

HCID 16222359HCID 16222359, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of 6-mercapto-2H-isoquinolin-1-one (50 mg, 0.28 mmol), 4-methane-sulphonyloxy-piperidine-1-carboxylic acid tert-butyl ester (117 mg, 0.42 mmol) and K2CO3 (64 mg, 0.46 mmol) in N, N-dimethylformamide (1.5 ml) was heated at 50° C. then left at ambient temperature overnight. Saturated aqueous sodium hydrogen carbonate was added to the mixture which was extracted with ethyl acetate (x 3). The combined organics were dried (Na2SO4) and concentrated in vacuo to give a residue. Flash chromatography of the residue using ethyl acetate:heptane (1:9 to 99:1) gave 4-(1-Oxo-1,2-dihydroisoquinolin-6-ylsulfanyl)piperidine-1-carboxylic acid tert-butyl ester (15 mg). A dichloromethane:trifluoroacetic acetic acid solution (7:3, 5 ml) was added to the 4-(1-Oxo-1,2-dihydroisoquinolin-6-ylsulfanyl)piperidine-1-carboxylic acid tert-butyl ester and the mixture stirred for 2 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 6-(piperidin-4-ylsulfanyl)-2H-isoquinolin-1-one, which was purified by prep-HPLC (2 mg), El-MS: m/z=261.1 [M+H]+.

Workup

  1. concentrationconcentrated in vacuo
  2. customto give a residue
  3. washeluted with 2M ammonia in methanol

Sources & evidence

ORD record
ord-42437ef5ec02478d82b90bed57782769
Source dataset
uspto-grants-2009_11
Patent number
US07618985B2

Reaction notes

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