反应详情

温度

110 °C

A mixture of crude N4-cyclopentyl-5-(3,6-dichloropyridazin-4-yl)pyrimidine-2,4-diamine (323) (0.27 g, 0.83 mmol) and sodium bicarbonate (0.065 mL, 1.7 mmol) in DMSO (10 mL) was heated in an oil bath at 110° C. for 11 h. Then the temperature was raised to 125° C. and stirred at this temperature for 200 min at which time LC-MS showed completion. Upon workup, the mixture was poured into ice and saturated NH4Cl aqueous solution and extracted with ethyl acetate (3×). The combined organics were washed with saturated NH4Cl aqueous solution (1×), dried over Na2SO4, and concentrated in vacuo. The residue was subjected to combi-flash column chromatography (methanol/DCM). The impure product thus obtained was subjected to subjected to preparative reverse phase HPLC (acetonitrile/H2O containing 0.1% TFA each). After lyophilization, 15 mg of compound 322 was obtained as a TFA salt as an off-white solid. 1H NMR (400 MHz, CD3OD) δ ppm 9.06 (1 H, s), 8.21 (1 H, s), 5.50 (1 H, quin, J=8.6 Hz), 2.43-2.60 (2 H, m), 1.99-2.25 (4 H, m), 1.71-1.89 (2 H, m). LCMS-ESI (POS), M/Z, M+1: Found 289.1.

1. temperatureThen the temperature was raised to 125° C.
2. extractionextracted with ethyl acetate (3×)
3. washThe combined organics were washed with saturated NH4Cl aqueous solution (1×)
4. dry with materialdried over Na2SO4
5. concentrationconcentrated in vacuo
6. customThe impure product thus obtained