4-Chloro-8-methylquinazoline

Phosphorous oxychloride (800 mL) was taken in a 2 L round bottom flask under nitrogen. To this was added 8-Methylquinazolin-4(3H)-one (125 g) in portions. The reactionminxture refluxed at 120 °C for 12h. Reaction completion was monitored by TLC and LCMS. After completion, the reactionminxture was cooled to RT and evaporated to dryness under reduced pressure. The resulted residue was dissolved in DCM (500 mL) and quenched slowly into an ice cold solution of saturated K2C03 with constant stirring. Then the organic layer was separated and washed with brine solution, dried over sodium sulfate and concentrated under vacuum to afford 4-chloro-8-methylquinazoline (120 g, 86percent) as yellow solid. This was taken for next step without further purification. MS: m/z = 179/18 1 [M+Hj.b. Preparation of Compound 12b To a solution of 8-methylquinazolin-4(3H)-one 12a (1.1 g, 6.92 mmol) in 155 ml ACN was added 10.1 mL POClTo a solution of 8-methylquinazolin-4(3H)-one 12a (1.1 g, 6.92 mmol) in 155 ml ACN was added 10.1 mE P0C13. The reaction mixture is refluxed until completion, cooled to room temperature. The solvent was removed under vacuum, and the crude product was purified in ISCO using Ethyl acetate:hexane solvent system to afford the pure product (430 mg, 35percent yield). 1H NMR (CDCl3, 400 MHz) ö 9.06 (s, 1-H), 8.12 (d, J=8.4 Hz, 1H), 7.80 (d, J=6.9 Hz, 1-H), 7.61 (m, 1H), 2.78 (s, 3H).

Molecular Weight:178.62
XLogP3:2.9
Hydrogen Bond Acceptor Count:2
Exact Mass:178.0297759
Monoisotopic Mass:178.0297759
Topological Polar Surface Area:25.8
Heavy Atom Count:12
Complexity:163
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes