Acetyl chloride → N-[3-chloro-6-(4-chlorophenyl)-7-(2,4-dichlorophenyl)-1-methyl-2-oxo-1,2-dihydro-1,8-naphthyridin-4-yl]acetamide

HRID 13834Notes

Reaction equation

HRID 13834 reaction equation
[H-].[Na+].C([Cl:6])(=O)C.[C:7]([N:10]([C:14]1[C:23]2[C:18](=[N:19][C:20]([C:31]3[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][C:32]=3[Cl:38])=[C:21]([C:24]3[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=3)[CH:22]=2)[N:17]([CH3:39])[C:16](=[O:40])[C:15]=1C)C(=O)C)(=[O:9])[CH3:8].C([O-])([O-])=O.[Cs+].[Cs+]>C1COCC1.CO.CCOC(C)=O.CN(C=O)C>[Cl:6][C:15]1[C:16](=[O:40])[N:17]([CH3:39])[C:18]2[C:23]([C:14]=1[NH:10][C:7](=[O:9])[CH3:8])=[CH:22][C:21]([C:24]1[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=1)=[C:20]([C:31]1[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][C:32]=1[Cl:38])[N:19]=2

Participants

9

Reactant 4

HCID 6367Acetyl chloride2×HCID 10796Cesium carbonateHCID 24758Sodium hydrideHCID 68718027N-acetyl-N-(7-(2,4-dichlorophenyl)-6-(4-chlorophenyl)-1,2-dihydro-1,3 dimethyl-2-oxo-1,8-naphthyridinyl)acetamide

Product 1

HCID 11420796N-[3-chloro-6-(4-chlorophenyl)-7-(2,4-dichlorophenyl)-1-methyl-2-oxo-1,2-dihydro-1,8-naphthyridin-4-yl]acetamide

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To the product to Step A (100 mg) in THF (1.5 mL) and DMF (0.3 mL) was added NaH (13 mg, 60% dispersion in mineral oil) at 0° C. After about 10 minutes acetyl chloride (61.4 μL) was added. An additional portion of acetyl chloride (30 μL) was added. Analysis of the reaction solution indicated a distribution between the 4-amino, 4-N-acetamide and 4-di-N-acetamide. The imide was cleaved by adding a solution of Cs2CO3 (about 200 mg) in methanol (about 5 mL). The reaction was diluted with EtOAc and washed with saturated aqueous NaHCO3 solution and then brine. The concentrated residue was purified by flash chromatography on silica gel gradient eluted with 0-100% EtOAc in hexane affording the title compound. HPLC/MS: 506.0 (M+1), 508.0 (M+3); Rt=4.50 min.

Workup

  1. washwashed with saturated aqueous NaHCO3 solution
  2. customThe concentrated residue was purified by flash chromatography on silica gel gradient
  3. washeluted with 0-100% EtOAc in hexane affording the title compound

Sources & evidence

ORD record
ord-138a78a32da7407b995236e5579a27a1
Source dataset
uspto-grants-2010_06
Patent number
US07728141B2

Reaction notes

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