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4-Cyano-3-methylbenzoic Acid is used as a reactant in the preparation of 5,6-dihydrobenzo[h]quinazolin-4(3H)-ones for the inhibition of group A streptococcal streptokinase expression.

To a tetrahydrofuran (THF, 100 ml) solution of 4-bromo-2-methylbenzonitrile (2.0 g, 10.2 mmol) was slowly added 2.5 M n-butyllithium solution (4.48 ml, 11.2 mmol) dropwise at -78 °C and under nitrogen protection. The reaction mixture was stirred continuously at -78 °C for 1 h and subsequently poured into a tetrahydrofuran (THF, 50 ml) solution pre-loaded with solid carbon dioxide (5 g). The reaction system was slowly warmed up to room temperature. After addition of water (200 ml), extraction was carried out with ether (3 times). The aqueous layer was acidified by adding concentrated hydrochloric acid and then extracted with chloroform (3 times). The chloroform extracts were combined, washed with water, dried over anhydrous magnesium sulfate (MgSO4) and finally concentrated under vacuum to give the white solid product 4-cyano-3-methylbenzoic acid (1.2 g, 73% yield).

[1] Bioorganic and Medicinal Chemistry Letters, 2004, vol. 14, # 17, p. 4585 - 4589
[2] Patent: EP1449844, 2004, A1. Location in patent: Page 21
[3] Patent: EP1512687, 2005, A1. Location in patent: Page/Page column 7
[4] Patent: WO2006/18443, 2006, A1. Location in patent: Page/Page column 21
[5] Patent: US6664249, 2003, B1. Location in patent: Page column 11