Реакция #42119

Уравнение реакции

NaH

N-(6-(2,4-dichlorophenyl)-5-(4-chlorophenyl)-3-cyanopyridin-2-yl)-2-methoxy-N-methylacetamide

product

3-Dimethylamino-1-(2,4-dichlorophenyl)-2-(4-chlorophenyl)prop-2-en-1-one

2-methoxyacetyl chloride

→

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

Растворители

THF

DMF

Условия реакции

Обработка

1. 1
   ДругоеAfter 15 minutes the reaction was quenched with acetic acid (0.2 mL)
2. 2
   workup.ADDITIONThe reaction was diluted with EtOAc
3. 3
   Промывкаwashed with saturated aqueous NaHCO3 solution and brine
4. 4
   workup.ADDITIONthe reaction was diluted with EtOAc
5. 5
   Промывкаwashed with saturated aqueous NaHCO3 solution and brine
6. 6
   ДругоеThe concentrated residue was purified by flash chromatography on silica gel gradient
7. 7
   Промывкаeluted with 0-100% EtOAc in hexane affording the title compound

Методика

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.

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