N(OCCC(C)C)=O.[Cl-:9].[Li+].N[C:12]1[C:13]([O:24][CH3:25])=[CH:14][C:15]([Cl:23])=[C:16]2[C:21]=1[C:20](=[O:22])[NH:19][CH2:18][CH2:17]2>C(#N)C.[Cu](Cl)Cl>[Cl:23][C:15]1[CH:14]=[C:13]([O:24][CH3:25])[C:12]([Cl:9])=[C:21]2[C:16]=1[CH2:17][CH2:18][NH:19][C:20]2=[O:22]Isopentyl nitrite (20 mL, 0.149 mol) was added dropwise to a heated (55° C.) suspension of copper (II) chloride (40 g, 0.298 mol) and lithium chloride (38 g, 0.905 mol) in acetonitrile (500 mL). The mixture was stirred at that temperature for 5 minutes, then 8-amino-5-chloro-7-methoxy-3,4-dihydroisoquinolin-1(2H)-one (296d, 20 g, 0.089 mol) was added in portions. After the addition was complete, stirring was continued at 55° C. for 45 minutes. The reaction mixture was cooled to room temperature, quenched with saturated aqueous ammonium chloride (300 mL), and extracted with ethyl acetate (4×200 mL). The combined organic layers were washed with aqueous ammonium chloride (200 mL) and brine (100 mL), dried over sodium sulfate, and concentrated under vacuum to give crude 5,8-dichloro-7-methoxy-3,4-dihydroisoquinolin-1(2H)-one (296e, 20 g, 90% purity, 92% yield) as a brown solid. MS: 245 [M+1].
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