4-Chloro-8-methylquinazoline → 8-Methylquinazoline

Temperature

45 °C

To a stirred solution of 4-Chloro-8-methylquinazoline (45 g, 0.252 mol) in DCM (700 mL) under N2 was added p-toluenesulfonylhydrazide (65.9 g, 0.353 mol) in portions. The reaction mixture was heated at 45° C. for 12 h. The reaction completion was monitored by LCMS and TLC. After completion, the reaction mixture was cooled to RT, the solvent evaporated to dryness and the resulted residue redissolved in EtOH (500 mL) and added 2N NaOH solution (300 mL) and refluxed for 6 h. After confirming by LCMS, the reaction mixture was cooled to RT and extracted with MTBE (3×600 mL). The combined organic layers were washed with brine solution, dried over sodium sulfate and concentrated under vacuum. The resulted residue was filtered through column chromatography using neutralized silica gel (60-120 mesh) and pet ether/ethyl acetate as an elutent to yield (15 g, 27% yield) of the titled compound as a low melting yellow solid. 1H NMR (DMSO-d6, 400 MHz) δ 9.54 (s, 1H), 9.31 (s, 1H), 7.97-7.94 (dd, J=8.8, 8.1 Hz, 1H), 7.87-7.84 (m, 1H), 7.65-7.62 (d, J=15.2 Hz, 1H), 2.67 (s, 3H).

1. temperatureAfter completion, the reaction mixture was cooled to RT
2. customthe solvent evaporated to dryness
3. dissolutionthe resulted residue redissolved in EtOH (500 mL)
4. additionadded 2N NaOH solution (300 mL)
5. temperaturerefluxed for 6 h
6. temperaturethe reaction mixture was cooled to RT
7. extractionextracted with MTBE (3×600 mL)
8. washThe combined organic layers were washed with brine solution
9. dry with materialdried over sodium sulfate
10. concentrationconcentrated under vacuum
11. filtrationThe resulted residue was filtered through column chromatography

ORD record

ord-b64038e70725411da2f4550dce7d0a37

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09139568B2