反应详情

A mixture of (2,6-dichloro-3-{[methyl-(1,2,3,4-tetrahydro-naphthalen-1-yl)-amino]-methyl}-pyridin-4-yl)-pyrrolidin-1-yl-methanone (200 mg, 0.48 mmol), 2,6-diethyl-phenyl boronic acid (85 mg, 0.48 mmol), Na2CO3 (2 M aqueous solution, 0.48 mL, 0.96 mmol), and Pd(PPh3)4 (50 mg) is refluxed in toluene (10 mL) for 18 hours and cooled to room temperature. Methylboronic acid (286 mg, 4.78 mmol), Na2CO3 (2 M aqueous solution, 0.48 mL, 0.96 mmol), and Pd(PPh3)4 (50 mg) are added to the mixture. The resulting mixture is refluxed in toluene for another 18 hours and then cooled to room temperature. Hexane (20 mL) and 1 N NaOH (2 mL) are added. The organic layer is separated, washed with brine, dried over sodium sulfate, and solvent removed. The crude product is purified by flash column (4:1 hexane:EtOAc) to give (6-(2,6-diethyl-phenyl)-2-methyl-3-{[methyl-(1,2,3,4-tetrahydro-naphthalen-1-yl)-amino]-methyl}-pyridin-4-yl)-pyrrolidin-1-yl-methanone. 1H NMR (CDCl3) 7.51 (m, 1H), 7.28 (m, 1H), 7.14-6.98 (m, 6H), 4.02-3.80 (m, 3H), 3.65 (m, 2H), 3.25 (m, 2H), 2.75-2.34 (m, 5H), 2.10 (m, 4H), 2.05-1.85 (m, 9H), 1.76 (m, 2H), 1.03 (t, 6H).

1. temperaturecooled to room temperature
2. customThe organic layer is separated
3. washwashed with brine
4. dry with materialdried over sodium sulfate, and solvent
5. customremoved
6. customThe crude product is purified by flash column (4:1 hexane:EtOAc)