反应详情

温度

100 °C

A vial is charged with 5-amino-2-methyl-nicotinic acid ethyl ester 8 (1.25 mmol), 2-chloro-5-(4-methoxy-phenyl)-pyrimidine 3 (1.25 mmol), Pd(OAc)2 (0.187 mmol), xanthphos (0.187 mmol), Cs2CO3 (1.25 mmol), and anhydrous 1,4-dioxane (8 mL). The vial is evacuated and refilled with N2 twice and the mixture is heated in an oil bath at 100° C. for 2 h. The vial is cooled down to rt and the reaction mixture is diluted with DCM, washed with 10% NH4Cl solution, brine and dried over Na2SO4. The solvent is removed under vacuum and the crude is purified by short silica gel chromatography using DCM:MeCN:MeOH=8:2.5:0.5 to afford 5-[5-(4-methoxy-phenyl)-pyrimidin-2-ylamino]-2-methyl-nicotinic acid ethyl ester 9 as pale yellow solid. 1H NMR (400 MHz, d6-DMSO) δ10.13 (s, 1H), 9.10 (d, J=4.0 Hz, 1H), 8.94 (s, 2H), 8.78 (d, J=4.0 Hz, 1H), 7.79-7.77 (m, 2H), 7.16-7.14 (m, 2H), 4.45 (q, J=8.0 Hz, 2H), 3.90 (s, 3H), 2.75 (s, 3H), 1.45 (t, J=8.0 Hz, 3H). MS (m/z) (M+1)+: 365.1.

1. customThe vial is evacuated
2. additionrefilled with N2 twice
3. temperatureThe vial is cooled down to rt
4. additionthe reaction mixture is diluted with DCM
5. washwashed with 10% NH4Cl solution, brine
6. dry with materialdried over Na2SO4
7. customThe solvent is removed under vacuum
8. customthe crude is purified by short silica gel chromatography