7-Bromo-2,4-dichloroquinazoline

205.0 g (0.84 mol) of 7-bromo-1H-benzo[d]-1, 3-oxazine-2, 4-dione were suspended in 1.26 l (12.59 mol) of phosphoryl chloride at room temperature, 71.34 ml (0.42 mol) of N-ethyldiisopropylamine were added, and the mixture was subsequently heated under reflux for 36 h. Conventional work-up gave 193.6 g of 7-bromo-2, 4-dichloroquinazoline; HPLC/MS (M+H)A solution of 26 (1.16 g, 4.81 mmol), POCl3 (4.49 mL, 48.1 mmol) and N, N-Diethylaniline (3.06 mL, 19.25 mmol) was heated at reflux for 4h. After cooling, the mixture was evaporated and the mixture was diluted with H2O and CHCl3. The organic layer was washed with H2O and sat. NaCl, then dried over MgSO4 and filtered. After removal of the solvent in vacuo, the residue was purified by silica gel column chromatography (CHCl3/hexane; 1:1 to 4:1) to give the title compound as slight yellow solid (1.02 g, 77percent). 1H NMR (CDCl3) δ = 7.83 (dd, 1H, J = 1.8, 8.9 Hz), 8.17 (dd, 1H, J = 0.4, 8.9 Hz), 8.20 (dd, 1H, J = 0.4, 1.8 Hz). MS:275.0 (M+)Step 5: 7-Bromo-2, 4-dichloro-quinazolineTo a 250 mL round bottom flask, 7-bromo-lH-quinazoline-2, 4-dione (10 g0.0413 mol) was charged. To the same flask POClTo a 250 mL round bottom flask, 7-bromo-1H-quinazoline-2, 4-dione (10 g 0.0413 mol) was added. To the same flask, POClA solution of 0.75 g (2.70 mmol) of compound 39 in 7.5 mL of NaOH solution (4% in water) and 2.5 mL of THF was stirred at RT for 2 h. The reaction was quenched with AcOH and extracted with three 20 mL portions of ethyl acetate. The combined organic extracts were concentrated to give compound 40. LC-MS: m/e = 259, 261 [M+H]+.General procedure: To a solution of 2, 4-dichlorofuro[3, 2-d]pyrimidine (la) (0.71 g, 3.74 mmol; CAS 956034- 07-4) in 2-Propanol (20 mL) was added DIPEA (1.63 mL, 9.36 mmol), 1-methyl-1H-imidazol-4-amine hydrochloride (0.5 g, 3.74 mmol) and heated at reflux for 24 h. The reaction mixture was concentrated in vacuum to dryness and the residue obtained was triturated with water. The solid obtained was collected by filtration and dried in vacuum to afford 2-chloro-N-(l-methyl-lH-imidazol-4-yl)furo[3, 2-d]pyrimidin-4-amine (lb) (550 mg, 59 % yield) as brown solid; NMR (300 MHz, DMSO-^) delta 10.89 (s, 1H, D20exchangeable), 8.35 (d, J = 2.1 Hz, 1H), 7.52 (d, J = 1.6 Hz, 1H), 7.39 (d, J = 1.3 Hz, 1H), 7.03 (d, J = 2.1 Hz, 1H), 3.71 (s, 3H); MS (ES+): 250.3 (M+l), 272.3, 274.3 (M+Na), (ES-): 248.2 (M-l).

Molecular Weight:277.93
XLogP3:4.2
Hydrogen Bond Acceptor Count:2
Exact Mass:275.88567
Monoisotopic Mass:275.88567
Topological Polar Surface Area:25.8
Heavy Atom Count:13
Complexity:193
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes