Methanol → HCID 68425418, compound

Participants

Reaction Conditions

Reaction Steps

The carbonylation reaction was conducted following the procedure described in J. Comb. 2003, 5, 350. To a solution of N-(2,6-dichloro-4-iodophenyl)-10-ethoxypyrido[4,3-c]-1,6-naphthyridin-6-amine (Example 152, Step 1) (130 mg, 0.39 mmol) and N-(2,6-dichloro-4-iodophenyl)-10-methoxypyrido[4,3-c]-1,6-naphthyridin-6-amine (Example 152, Step 1) (66 mg, 0.13 mol) in methanol (5 mL) were added dimethylamino pyridine (96 mg, 0.78 mmol), diisopropylethylamine (137 uL, 0.78 mmol), molybdenumhexacarbonyl (106 mg, 0.39 mmol) and palladium (II) acetate (9 mg, 0.39 mmol). The solution was heated in a microwave reactor at 150° C. for 15 min. The black solution was extracted with EtOAc and water, dried with MgSO4, filtered, and concentrated under reduced pressure. Purification by chromatography on silica gel (100% hexanes to 100% EtOAc) afforded methyl 3,5-dichloro-4-[(10-ethoxypyrido[4,3-c]-1,6-naphthyridin-6-yl)amino]benzoate and methyl 3,5-dichloro-4-[(10-methoxypyrido[4,3-c]-1,6-naphthyridin-6-yl)amino]benzoate. The mixture of esters (117 mg, 0.27 mmol) were suspended in CHCl3 (5 mL) followed by addition of BBr3 (1.91 mL, 1.91 mmol). The reaction mixture was heated to 85° C. for 45 min. After cooling to room temperature, the solution was extracted with EtOAc and saturated NaHCO3, dried with MgSO4, filtered, and concentrated. Purification by chromatography on silica gel (100% CH2Cl2 to 70% CH2Cl2/30% MeOH) afforded the title compound.

Provenance & Evidence