956010-88-1

1H-pyrazolo[3,4-b]pyridine-3-carbonitrile can be used to prepare SGC stimulants for the treatment of central nervous system disorders.

General procedure for the synthesis of 1H-pyrazolo[3,4-b]pyridine-3-carbonitrile from 3-(trifluoromethyl)-1H-pyrazolo[3,4-B]pyridine: 3-(Trifluoromethyl)-1H-pyrazolo[3,4-B]pyridine (500 mg, 2.67 mmol) was suspended in 33% ammonia solution (10 mL). The mixture was placed in a sealed tube and heated to 140 °C using microwave and maintained for 10 min. Upon completion of the reaction, the volatiles were evaporated. Ethyl acetate (100 mL) and tert-butyl methyl ether (25 mL) were added to the residue and the mixture was heated to 70 °C. The mixture was filtered while hot and the residue was washed with tert-butyl methyl ether. The filtrates were combined and evaporated to afford 1H-pyrazolo[3,4-b]pyridine-3-carbonitrile as a light yellow solid (389 mg, 90% yield), with trace amounts of the corresponding primary amide in the product. The structure of the product was determined by 1H NMR (400 MHz, DMSO-d6): δ 7.47 (dd, J = 8.2,4.5 Hz, 1H), 8.46 (dd, J = 8.2,1.5 Hz, 1H), 8.73 (dd, J = 4.5,1.5 Hz, 1H), 15.02 (br s, 1H); 13C NMR (125 MHz. DMSO-d6): δ 113.5,115.5,116.9,119.6,128.7,150.9,151.0 confirmed. High-resolution mass spectrometry (HRMS) analysis results: calculated value C7H4N4 [M]+: 144.0436; measured value: 144.0430.

[1] Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 5, p. 1197 - 1200
[2] Tetrahedron, 2015, vol. 71, # 34, p. 5597 - 5601
[3] Patent: US2010/113507, 2010, A1. Location in patent: Page/Page column 9
[4] Patent: US2010/4235, 2010, A1. Location in patent: Page/Page column 15