Dichloromethane → 5-chloro-8-fluoro,2-methyl-3-[(4-methylphenyl)sulfonyl]pyrrolo[2',3':4,5]pyrimido[6,1-b]quinazolin-7(3H)-one HCl salt

Beteiligte Stoffe

Reaktionsbedingungen

Reaktionsschritte

To a suspension of 2,4-dichloro-5-methyl-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidine (535 mg, 1.50 mmol) and 2-amino-6-fluorobenzoic acid (233 mg, 1.50 mmol) in isopropanol (5 mL) was added diisopropylethylamine (971 mg, 7.51 mmol) and the mixture was heated at 85° C. for ˜48 h. At this time the reaction was diluted with ethyl acetate (100 ml) and washed with a solution of 1N HCl, a saturated solution of sodium bicarbonate and a saturated solution of NaCl, then dried over sodium sulfate. Solvents were removed under reduced pressure to afford a solid containing about 60% 2-({2-chloro-6-methyl-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-6-fluorobenzoic acid (726 mg, 1.52 mmol). This material was dissolved in THF (10 mL) and DMF (few drops) and a solution of 2M oxalyl chloride in dichloromethane (0.90 mL, 1.80 mmol) was added dropwise. LCMS analysis indicated a small amount of starting material remained so an additional 0.1 eq of oxalyl chloride was added. The reaction mixture was cooled in an ice bath and filtered via a buchner funnel and the solid washed with THF. The solid was dried under reduced pressure to afford 5-chloro-8-fluoro-2-methyl-3-[(4-methylphenyl)sulfonyl]pyrrolo[2′,3′:4,5]pyrimido[6,1-b]quinazolin-7(3H)-one HCl salt (280 mg, 0.0.57 mmol). ESIMS (M+H)+=457

Herkunft & Nachweise