6-Bromo-4-chloroquinazoline

6-Bromo-3H-quinazolin-4-one (20g, 89 mmol) was suspended in 140 ml. of POCI6-Bromo-3H-quinazolin-4-one (20g, 89 mmol) was suspended in 140 mL of POCI6-Bromo-4-chloro-quinazoline then, In a dioxane solution containing 6-bromo-3H-quinazolin-4-one (B, 15.0 g, 66.7 mmol, 1.0 equiv)Was added phosphorus oxychloride (20.0 ml, d = 1.67, 33.4 g, 219 mmol, 3.3 equiv), Followed by the addition of triethylamine (30.0 mL, d = 0.726, 21.8 g, 215 mmol)The mixture was heated under reflux for 12 hours, Until the solution drops to room temperature, Pour it into a mixed solution containing ice and water.The precipitate obtained after filtration was washed with 100 ml of water, And dried to give 6-bromo-4-chloro-quinazoline (C, 15.4 g, 63.2 mmol)Yield 95percentExample 3. Synthesis of 6-bromo-4-chloroquinazoline (4): To the solution of 6-bromoquinazolin-4-oI (3, 1 g, 4.44 mmol) in phosphoryl chloride (5 mL) was refluxed for 6 hat 120 °C. The mixture was cooled to room temperature and poured into ice-watercontaining sodium bicarbonate to quench excess phosphoryl chloride. The mixture wasextracted with dichloromethane (3 x 100 ml) and the solvent was evaporated to get the 6-bromo-4-chloroquinazoline 4 as a light yellow solid. Yield: 92percent, light yellow solid, m. p. 273-275 °C; 1H NMR (CDCI3, 500 MHz): O 9.07 (s, IH), 8.44 (d, IH, J= 2.0 Hz), 8.04 (d, 1H, J2.0 Hz), 7.96 (d, IH, J = 8.9 Hz); HRMS: m/z 224.9633 calcd for C8H6BrN2O + H(224.9664).General procedure: To the suspension of 6-bromopyrido[2, 3-d]pyrimidin-4-ol (3) (15.0 g, 0.066 mol) in thionyl chloride 150 mL was added a few drops of DMF, then the mixture was stirred at reflux for 6 h. Equipped with a blender, Reflux condenser 250mL three-necked flask, 15 g (0.067 mol) of 6-bromo-4 (3H) -quinazolinone was added, 150 mL (2.1 mol) of thionyl chloride was added, 3-4 drops of DMF, Heating reflux, After about 1h the reaction was clarified, Continue to react 5h, Distillation recovery of thionyl chloride, The residual thionyl chloride was distilled off under reduced pressure, Continue to join 50mL dichloromethane distillation residual thionyl chloride out, Repeated three timesFinally, 180 mL of ethyl acetate was heated to reflux for several minutes, Place to room temperature, filter, Vacuum dried, Got light yellow needles solid 12.2g, Yield 75percent.General procedure: The solution of 6-bromoquinazolin-4-ol (12, 1 g, 4.44 mmol) or6, 7-dimethoxyquinazolin-4-ol (17, 1 g, 4.13 mmol) in phosphorousoxy chloride (5 mL) was refluxed for 6 h at 120 C. The mixture was cooled to room temperature and poured into ice-water containingsodium bicarbonate to quench phosphorous oxychloride. The mixture was extracted with dichloromethane (3 100 ml) and thesolvent was evaporated to get chlorinated products 13 or 18.4.4.1. 6-Bromo-4-chloroquinazoline (13)Yield: 74percent; light yellow solid; m.p. 161e163 C; 1H NMR (CDCl3, 500 MHz): d 9.07 (s, 1H), 8.44 (d, 1H, J 2.0 Hz), 8.05 (dd, 1H, J 8.9, 2.2 Hz), 7.96 (d, 1H, J 8.9 Hz); IR (CHCl3): nmax 2922, 1632, 1559, 1546, 1474, 1461, 1388, 1360, 1241, 1160, 1019 cm1; HR-ESIMS: m/z242.9326 calcd for C8H4BrClN2H (242.9319).Synthesis of compound 2.2. To a mixture of 6-bromoquinazolin-4-ol, compound 2.1 (1.2 g, 5.33 mmol, 1.00 equiv) in POClFormamide (4 ml) was added to methyl 2-amino-5-bromo-benzoate (400 mg), and the mixture was stirred with a microwave reactor at 220°C for 20 min. The above reaction was carried out using the same amount of starting materials by additional two batches. The reaction mixtures were cooled to room temperature and were combined together. The precipitated crystal was collected by filtration and was washed with ether. The crystal (968 mg) thus obtained as such was used in the next reaction without further purification. A part (300 mg) of the crystal obtained above was suspended in diisopropylethylamine (1.16 ml), phosphorus oxychloride (0.62 ml) was added to the suspension, and the mixture was stirred at 100°C for 2 hr. The solvent was removed by distillation under the reduced pressure, and water was added to the residue under ice cooling. The aqueous layer was neutralized with an aqueous sodium hydrogencarbonate solution, and the organic layer was extracted with ethyl acetate. The ethyl acetate layer was then washed with water and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by thin layer chromatography with a methanol-chloroform system to give 6-bromo-4-chloro-quinazoline (58 mg, yield 18percent).

Molecular Weight:243.49
XLogP3:3.2
Hydrogen Bond Acceptor Count:2
Exact Mass:241.92464
Monoisotopic Mass:241.92464
Topological Polar Surface Area:25.8
Heavy Atom Count:12
Complexity:167
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes