Sodium Hypochlorite → HCID 118558158, compound

HRID 927281Notes

Reaction equation

HRID 927281 reaction equation
[Cl:1][O-].[Na+].[F:4][C:5]1[CH:10]=[CH:9][C:8]([N:11]2[C:20]([CH2:21][CH2:22][CH2:23][CH2:24][C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])=[CH:19][C:18]3[C:13](=[CH:14][CH:15]=[C:16](/[CH:32]=[N:33]/[OH:34])[CH:17]=3)[C:12]2=[O:35])=[CH:7][CH:6]=1.[F:36][C:37]1[CH:48]=[CH:47][C:40]2[N:41]=[C:42]([C:44]([CH3:46])=[CH2:45])[O:43][C:39]=2[CH:38]=1>ClCCl>[Cl:1][C:19]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([C:32]3[CH2:45][C:44]([C:42]4[O:43][C:39]5[CH:38]=[C:37]([F:36])[CH:48]=[CH:47][C:40]=5[N:41]=4)([CH3:46])[O:34][N:33]=3)[CH:17]=2)[C:12](=[O:35])[N:11]([C:8]2[CH:9]=[CH:10][C:5]([F:4])=[CH:6][CH:7]=2)[C:20]=1[CH2:21][CH2:22][CH2:23][CH2:24][C:25]([O:27][C:28]([CH3:29])([CH3:30])[CH3:31])=[O:26]

Participants

5

Reactant 3

HCID 23665760Sodium HypochloriteHCID 68278593HCID 68278593, compoundHCID 172922594HCID 172922594, compound

Product 1

HCID 118558158HCID 118558158, compoundYield 32.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Sodium hypochlorite (1.408 mL, 0.912 mmol) was added to a stirred, room temperature mixture of (E)-tert-butyl 5-(2-(4-fluorophenyl)-6-((hydroxyimino)methyl)-1-oxo-1,2-dihydroisoquinolin-3-yl)pentanoate (100 mg, 0.228 mmol) and 6-fluoro-2-(prop-1-en-2-yl)benzo[d]oxazole (40.4 mg, 0.228 mmol) in dichloromethane (2 mL) and the mixture was stirred at room temperature for overnight. The reaction was checked with LCMS and starting material was all consumed. The mixture was diluted with dichloromethane (10 mL), washed with aqueous sodium hydrogen carbonate (saturated, 1×6 mL), dried (MgSO4), filtered and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel, eluting with EtOAc/isohexane=50% to give tert-butyl 5-(4-chloro-6-(5-(6-fluorobenzo[d]oxazol-2-yl)-5-methyl-4,5-dihydroisoxazol-3-yl)-2-(4-fluorophenyl)-1-oxo-1,2-dihydroisoquinolin-3-yl)pentanoate (48 mg, 0.074 mmol) as a yellow solid, 648.0 (M+H+); and tert-butyl 5-(6-(5-(6-fluorobenzo[d]oxazol-2-yl)-5-methyl-4,5-dihydroisoxazol-3-yl)-2-(4-fluorophenyl)-1-oxo-1,2-dihydroisoquinolin-3-yl)pentanoate (26 mg, 0.042 mmol) as a yellow solid which were deprotected with TFA as in Example 5.1 to give Examples 6.1 and 6.2 respectively.

Workup

  1. washwashed with aqueous sodium hydrogen carbonate (saturated, 1×6 mL)
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. customthe solvent was evaporated under reduced pressure
  5. customThe residue was purified by column chromatography on silica gel
  6. washeluting with EtOAc/isohexane=50%

Sources & evidence

ORD record
ord-ad595e9062b6492b92eb8573121bf4dc
Source dataset
uspto-grants-2016_03
Patent number
US09290454B2

Reaction notes

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