反应详情

A mixture of 4,6-dichloropyrido[3,2-d]pyrimidine (Intermediate 1, step D) (0.100 g, 0.500 mmol), cyclobutanamine (0.047 ml, 0.550 mmol), PdCl2(dppf)-CH2Cl2Adduct (4.08 mg, 5.00 mmol) and sodium tert-butoxide (0.096 g, 1.00 mmol) in dioxane (2.50 ml) was refluxed for 4 hours. After cooling to room temperature, the reaction mixture was filtered through a Celite pad and washed with CH2Cl2. The filtrate was concentrated in vacuo. The residue was purified by column chromatography on SiO2 (Hex:EtOAc=1:1) to give 6-chloro-N-cyclobutylpyrido[3,2-d]pyrimidin-4-amine (0.098 g, 84%) as a yellow solid. 1H-NMR (CDCl3, Varian 400 MHz) δ 1.79-1.89 (2H, m), 2.06-2.17 (2H, m), 2.48-2.56 (2H, m), 4.71-4.82 (1H, m), 7.11 (1H, brs), 7.61 (1H, d, J=8.8 Hz), 8.03 (1H, d, J=8.8 Hz), 8.61 (1H, s).

1. temperaturewas refluxed for 4 hours
2. filtrationthe reaction mixture was filtered through a Celite pad
3. washwashed with CH2Cl2
4. concentrationThe filtrate was concentrated in vacuo
5. customThe residue was purified by column chromatography on SiO2 (Hex:EtOAc=1:1)