Synthesis
General procedure for the synthesis of 4-chloro-7-methoxy-6-ol from 6-acetoxy-4-chloro-7-methoxyquinazoline: 4-chloro-7-methoxyquinazolin-6-yl acetate (prepared according to the method described in Example 25-5 of WO01/66099, 10.1 g, 40 mmol) was suspended in 6 N methanol-ammonia solution (200 mL) and stirred at room temperature for 90 minutes at room temperature. Upon completion of the reaction, the solvent was removed by evaporation under vacuum. Water was added to the residue and the resulting suspension was filtered. The collected solids were washed sequentially with water and ether and subsequently dried at high temperature. Finally, vacuum drying in the presence of phosphorus pentoxide gave 4-chloro-7-methoxyquinazolin-6-ol (7.9 g, 94% yield). The NMR hydrogen spectrum (DMSO-d6) data were as follows: δ 4.02 (s, 3H), 7.40 (s, 1H), 7.43 (s, 1H), 8.81 (s, 1H).
References
[1] Patent: WO2005/26151, 2005, A1. Location in patent: Page/Page column 124
[2] European Journal of Medicinal Chemistry, 2018, vol. 147, p. 130 - 149
[3] Patent: CN106986895, 2017, A. Location in patent: Paragraph 0072; 0073; 0074; 0075; 0076
[4] Patent: CN105384699, 2016, A. Location in patent: Paragraph 0032; 0033
[5] Patent: CN105418517, 2016, A. Location in patent: Paragraph 0026; 0030; 0031
