Synthesis
General method 1: 4-chloroquinazoline derivatives were synthesized as target products by the introduction of alkyl amino side chains. Specifically, this includes the preparation of 4-chloro-6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinazoline, 4-chloro-7-methoxy-6-[3-(4-methylpiperazin-1-yl)propoxy]quinazoline, and 4-chloro-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazoline.
Step 1: Methyl vanillate or methyl isovanillate (7.29 g, 40 mmol) was dissolved in 25 mL of dimethylformamide, followed by the addition of potassium carbonate (8.29 g, 60 mmol) and benzyl bromide (5.26 mL, 44 mmol). The reaction mixture was heated to 100 °C and maintained at this temperature for 3 hours. After completion of the reaction, it was cooled to room temperature, diluted with water and the product was extracted several times with ethyl acetate. The organic phases were combined and washed sequentially with water and brine. The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure to remove the solvent to obtain methyl 4-benzyloxy-3-methoxybenzoate or methyl 3-benzyloxy-4-methoxybenzoate, and the product could be used for subsequent reaction without further purification.
References
[1] Patent: US2007/21446, 2007, A1. Location in patent: Page/Page column 14
[2] Patent: EP1785420, 2007, A1. Location in patent: Page/Page column 18
[3] Bioorganic and Medicinal Chemistry, 2009, vol. 17, # 18, p. 6728 - 6737
[4] Patent: EP1746096, 2007, A1. Location in patent: Page/Page column 23
[5] ChemMedChem, 2016, vol. 11, # 20, p. 2327 - 2338
