Methyl Acrylate → HCID 57657221, compound

Participants

Reaction Conditions

Reaction Steps

A 50-mL thick walled glass vessel was charged with palladium (II) acetate (67 mg, 0.3 mmol), acetonitrile (2 mL), methyl acrylate (0.26 g, 3.0 mmol), triethylamine (0.9 g, 9.0 mmol), tri-o-tolylphosphine (0.18 g, 0.6 mmol) and 7-bromo-1-[4-(1,1-dioxidoisothiazolidin-2-yl)butyl]-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-4-amine (U.S. Patent Application Publication No. US 2004/0147543 Example 152-156, 1.5 g, 3.0 mmol). An additional 13 mL of acetonitrile was added. The reaction mixture was purged with nitrogen then heated to 90° C. The turbid orange mixture was maintained at 90° C. overnight. Anhydrous DMF (30 mL) was added to dissolve the 7-bromoquinoline starting material. The reaction was then heated at 120° C. overnight. The reaction mixture was filtered to remove the catalyst then concentrated to dryness. The desired product was isolated by column chromatography on silica gel (eluting with a gradient of 2%-8% methanol in dichloromethane). The resulting peach solid was taken up in saturated potassium carbonate solution and dichloromethane and stirred overnight at ambient temperature. The organic layer was separated and concentrated to dryness. The residue was recrystallized from acetonitrile to yield 0.65 g of Methyl(2E)-3-[4-amino-1-[4-(1,1-dioxidoisothiazolidin-2-yl)butyl]-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-7-yl]prop-2-enoate as a pale yellow solid, mp 162-163° C.

Provenance & Evidence