Acetic Acid → HCID 16222462, compound

HRID 1436005Notes

Reaction equation

HRID 1436005 reaction equation
ClCCl.C(O)(=O)C.C(OC([N:15]1[CH2:20][CH2:19][CH2:18][C@H:17]([O:21][C:22]2[CH:23]=[C:24]3[C:29](=[CH:30][CH:31]=2)[C:28](=[O:32])[NH:27][CH:26]=[C:25]3[Br:33])[CH2:16]1)=O)(C)(C)C>CO>[Br:33][C:25]1[C:24]2[C:29](=[CH:30][CH:31]=[C:22]([O:21][C@H:17]3[CH2:18][CH2:19][CH2:20][NH:15][CH2:16]3)[CH:23]=2)[C:28](=[O:32])[NH:27][CH:26]=1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 6344DichloromethaneHCID 68875660HCID 68875660, compound

Product 1

HCID 16222462HCID 16222462, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of (S)-3-(oxo-1,2-dihydroisoquinolin-6-yloxy)piperidine-1-carboxylic acid tert-butyl ester (1 g, 2.9 mmol) and N-bromosuccinamide (516 mg, 2.9 mmol) in acetonitrile was stirred overnight at ambient temperature. The mixture was absorbed onto silica and flash chromatography (eluent: ethyl acetate) to give (S)-3-(4-bromo-1-oxo-1,2-dihydroisoquinblin-6-yloxy)piperidine-1-carboxylic acid tert-butyl ester (700 mg). Dichloromethane and trifluoroacetic acetic acid (3:1, 20 ml) were added to (S)-3-(4-bromo-1-oxo-1,2-dihydroisoquinolin-6-yloxy)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 (S)-4-bromo-6-(piperidin-3-yloxy)-2H-isoquinolin-1-one (530 mg), which was purified by prep-HPLC, El-MS: m/z=325.5 [M+H]+.

Workup

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

Sources & evidence

ORD record
ord-e2e1eedcd2734b7fa19b488c4caf8e07
Source dataset
uspto-grants-2009_11
Patent number
US07618985B2

Reaction notes

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