反应详情

Triethylamine (0.5 mL) was added to a mixture of O-methylhydroxylamine hydrochloride (220 mg) and 2-(3-imidazol-1-yl-propylamino)-8-indan-5-yl-5-oxo-5,8-dihydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid ethyl ester (Example 3 Step A, 3.0 mg, 0.006 mmol) in 0.5 mL of methanol. The reaction mixture was kept in a sealed tube at 110° C. for 2 days with stirring. After cooling to room temperature the solution was diluted with water and extracted with dichloromethane. The crude product, after concentration, was loaded to HPLC for purification (32 mL/min 5-100% MeCN/H2O gradient over 10 min). 2-(3-Imidazol-1-yl-propylamino)-8-indan-5-yl-5-oxo-5,8-dihydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid methoxy-amide was obtained as a white solid (1.9 mg, 65%). 1H NMR (400 MHz, CDCl3) δ (ppm): 11.98 (br, 1H), 9.28 (s, 1H), 8.75 (s, 1H), 7.32 (d, J=7.8 Hz, 1H), 7.21 (s, 1H), 7.14 (d, J=7.8 Hz, 1H), 7.03 (br, 2), 6.74 (s, 1H), 5.80 (br, 1H), 3.89 (s, 3H), 3.00 (m, 8H), 2.17 (m, 2H), 1.92 (m, 2H). Mass Spectrum (LCMS, ESI pos.) Calcd. For C24H25N7O3: 460.20 (M+H). Found. 460.2.

1. extractionextracted with dichloromethane
2. concentrationThe crude product, after concentration
3. customwas loaded to HPLC for purification (32 mL/min 5-100% MeCN/H2O gradient over 10 min)