تفاعل #40624

معادلة التفاعل

Triethylamine

O-methylhydroxylamine hydrochloride

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

→

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

المذيبات

water

methanol

ظروف التفاعل

المعالجة

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

الإجراء التجريبي

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.

المصدر