4-CHLORO-6-FLUOROQUINAZOLINE

A mixture of compound 3 (1.64 g, 0.01 mol) in phosphorus oxychloride (0.05 mol, 7.5 mL) andphosphorous pentachloride (0.03 mol, 6 g) was heated on a water bath for 2 hr. The reaction mixturewas cooled and poured slowly onto crushed ice. The resulted precipitate was filtered off, washed withwater, dried, and purified by column chromatography with hexanes/ethyl acetate to afford the desiredproduct. Yield 65percent; mp: 140–142 °C; 1H-NMR (DMSO-d6, 300 MHz) δ 8.12 (s, 1H, ArH), 7.47 (dd, 1H, J = 7.9 Hz and 2.8 Hz, ArH), 7.53 (dd, 1H, J = 8.6 Hz and 5.1 Hz, ArH), 7.62 (s, 1H, ArH); C8H4ClFN2(182): MS (ESI) m/z 183 [M + 1]The crude product 172-2(0.82g, 5 mmol) is mixed with thionyl dichloride (12.0 g, 0.1 mol) and catalytic amount of anhydrous DMF (0.5 mL), then heated at about 100 °C for16 hours. After the reaction is complete, the mixture is cooled and excess thionyl dichlorideis removed by rotary evaporation. Dichloromethane (10 mL) is added to dissolve the solid, and then petroleum ether (5OmL) is added to solution. The mixture is filtrated, washed with ether and petroleum ether, dried and purified by silica gel chromatography (PE:AE=1 :1) to afford compound 172-3 as a white solid (0.75 g, yield: 82percent).4-Chloro-6-fluoroquinazoline (200.0 mg, 1.10 mmol) and 2-(4-nitrophenyl)ethan-1-amine hydrochloride (222.0 mg, 1.10 mmol) were dissolved in iPrOH (5.5 mL) and cooled to 0C, and Et3N (457.0 muL, 3.30 mmol) was added thereto. The reaction mixture was stirred at 100C for 15 hours and distilled under reduced pressure. The residue was extracted with EtOAc. The organic layer was washed with brine, dried with Na2SO4, filtered and distilled under reduced pressure. The residue was purified by column chromatography (CH2Cl2:MeOH=30:1) on silica. The fractions containing the product were collected and evaporated to obtain the white solid compound, 6-fluoro-N-(4-nitrophenethyl)quinazolin-4-amine (270.0 mg, 78%).[693][694]1H NMR (300 MHz, DMSO-d6) delta = 8.48 (s, 1H), 8.39 - 8.30 (m, 1H), 8.16 (d, J= 8.4 Hz, 2H), 8.09 - 8.00 (m, 1H), 7.80 - 7.62 (m, 2H), 7.55 (d, J= 8.4 Hz, 2H), 3.82 (q, J= 6.9 Hz, 2H), 3.19 - 3.06 (m, 2H)[695]LC/MS ESI (+): 313 (M+1) 2 [1] (2.00 g, 10.95 mmol) and 1, 4-dioxane (20 mL) were added into a round bottom flask and stirred for 5 min, followed by addition of methyl 4-piperidinecarboxylate (1.63 mL, 12.05 mmol) to the above mixture. The resulting mixture was heated to reflux for 7 h and then cooled to room temperature. The formed precipitate was filtered off, washed with 1, 4-dioxane and dried to give 3 as a white solid. Yield: 77.3%;

Molecular Weight:182.58
XLogP3:2.6
Hydrogen Bond Acceptor Count:3
Exact Mass:182.0047040
Monoisotopic Mass:182.0047040
Topological Polar Surface Area:25.8
Heavy Atom Count:12
Complexity:167
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes