Sodium hydride → N-(6-(4-chlorophenyl)-7-(2,4-dichlorophenyl)-3-methoxy-1-methyl-2-oxo-1,2-dihydro-1,8-naphthyridin-4-yl)acetamide

HRID 13841Notes

Reaction equation

HRID 13841 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:14]=[C:13]([N:15]([CH3:21])[C:16](=[O:20])[CH2:17][O:18][CH3:19])[C:12]([C:22]#[N:23])=[CH:11][C:10]=1[C:24]1[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=1.CN(C)C=[C:34](C1C=CC(Cl)=CC=1)[C:35](C1C=CC(Cl)=CC=1Cl)=[O:36].COCC(Cl)=O.[H-].[Na+]>CN(C=O)C.C1COCC1>[Cl:30][C:27]1[CH:26]=[CH:25][C:24]([C:10]2[CH:11]=[C:12]3[C:13](=[N:14][C:9]=2[C:3]2[CH:4]=[CH:5][C:6]([Cl:8])=[CH:7][C:2]=2[Cl:1])[N:15]([CH3:21])[C:16](=[O:20])[C:17]([O:18][CH3:19])=[C:22]3[NH:23][C:35](=[O:36])[CH3:34])=[CH:29][CH:28]=1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 96623Methoxyacetyl chlorideHCID 670199243-Dimethylamino-1-(2,4-dichlorophenyl)-2-(4-chlorophenyl)prop-2-en-1-oneHCID 68715386N-(6-(2,4-dichlorophenyl)-5-(4-chlorophenyl)-3-cyanopyridin-2-yl)-2-methoxy-N-methylacetamide

Product 1

HCID 11443469N-(6-(4-chlorophenyl)-7-(2,4-dichlorophenyl)-3-methoxy-1-methyl-2-oxo-1,2-dihydro-1,8-naphthyridin-4-yl)acetamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

N-(6-(2,4-dichlorophenyl)-5-(4-chlorophenyl)-3-cyanopyridin-2-yl)-2-methoxy-N-methylacetamide (368.5 mg, prepared by the reaction of the product of Step A Example 1 with 2-methoxyacetyl chloride using the conditions of EXAMPLE 62 Step A) was combined with THF (5 mL), DMF (0.5 mL) and NaH (48 mg, 60% dispersion in mineral oil). After 15 minutes the reaction was quenched with acetic acid (0.2 mL). The reaction was diluted with EtOAc and washed with saturated aqueous NaHCO3 solution and brine. The concentrated residue was suspended in THF (4 mL), DMF (0.5 mL) and acetyl chloride (0.5 mL). Once LC/MS indicated the acylation was complete, the reaction was diluted with EtOAc and washed with saturated aqueous NaHCO3 solution and 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: 502.0 (M+1), 504.00 (M+3); Rt=3.92 min.

Workup

  1. customAfter 15 minutes the reaction was quenched with acetic acid (0.2 mL)
  2. additionThe reaction was diluted with EtOAc
  3. washwashed with saturated aqueous NaHCO3 solution and brine
  4. additionthe reaction was diluted with EtOAc
  5. washwashed with saturated aqueous NaHCO3 solution and brine
  6. customThe concentrated residue was purified by flash chromatography on silica gel gradient
  7. washeluted with 0-100% EtOAc in hexane affording the title compound

Sources & evidence

ORD record
ord-8690ddf6049440b4af4a1df9451bbe81
Source dataset
uspto-grants-2010_06
Patent number
US07728141B2

Reaction notes

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