Synthesis
Concentrated hydrochloric acid (4.16 mL, 49.9 mmol) was slowly added to a mixed solution containing commercially available 2-amino-5-methylbenzamide (5.00 g, 33.3 mmol) and trimethyl orthoformate (51.0 mL, 466 mmol) at 0 °C. The reaction mixture was stirred continuously for 2 hours at room temperature. Upon completion of the reaction, the solvent was removed by distillation under reduced pressure and the residue obtained was diluted with distilled water and neutralized with 2 M aqueous sodium hydroxide solution to neutral. Subsequently, the precipitated solid product was collected by filtration and washed sequentially with distilled water, methanol, and ether to finally obtain 6-methyl-4-hydroxyquinazoline (15) as a white powdery solid (4.33 g, 81% yield). The structure of the product was confirmed by 1H NMR (300 MHz, DMSO-d6): δ 2.44 (3H, s), 7.57 (1H, d, J = 8.4 Hz), 7.62-7.66 (1H, m), 7.91-7.93 (1H, m), 8.03 (1H, s), 12.2 (1H, bs).
References
[1] Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 19, p. 5487 - 5505
[2] Bioorganic and Medicinal Chemistry Letters, 2001, vol. 11, # 4, p. 545 - 548
[3] Bioorganic and Medicinal Chemistry, 2003, vol. 11, # 3, p. 383 - 391
