AM-6538 synthesis

Yield: 74.6%

Reaction Conditions:

with silver nitrate in acetonitrile for 2 h;Heating;

Steps:

2
To a stirred solution of compound 5 [1-(2,4-dichlorophenyl)-5-(4-(4-iodobut-1- ynyl)phenyl)-4-methyl-N-(piperidin-1-yl)-1 H-pyrazole-3-carboxamide](60 mg, 0.9 mmol) taken in acetonitrile (20 ml) and to that silver nitrate (33.5 mg, 0.19 mmol) was added. The reaction mixture was heated for 2 hours. After cooling to RT, the precipitate was filtered. The filtrate was concentrated to give an oily residue which was subsequently dissolved in dichloromethane (20 ml). This was washed with 2x5 ml water and the organic layer was dried over anhydrous sodium sulfate, filtered, and evaporated. Flash column chromatography on silica gel with petroleum ether/ethyl acetate (1 :1) gave compound 2 (40 mg, 74.6% yield) as a white solid. 1H NMR (500 MHz, CDCI₃-d) 7.65 (s, 1 H), 7.43 (s, 1 H), 7.36 (d, J = 8.30 Hz, 2H), 7.29 - 7.33 (m, 2H), 7.07 (d, J = 8.30 Hz, 2H), 4.64 (t, J = 6.84 Hz, 2H), 2.74 - 3.02 (m, 6H), 2.39 (s, 3H), 1.69 - 1.90 (m, 4H), 1.45 (br. s., 2H)

References:

UNIVERSITY OF CONNECTICUT;MAKRIYANNIS, Alexandros;VEMURI, Venkata, Kiran;THOTAPALLY, Rajesh;OLSZEWSKA, Teresa WO2010/104488, 2010, A1 Location in patent:Page/Page column 61