7-FLUORO-1-H-BENZO[D][1,3]OXAZINE-2,4-DIONE

Step A — Synthesis of Intermediate Compound Int-4a: To a solution of 2-amino-4-fluorobenzoic acid (15.5 g, 100 mmol) in THF (200 mL) cooled to 0 °C was added triphosgene (27.9 g, 105 mmol). After heating at 50 °C for 6hours, the solvent was concentrated in vacuo. The crude residue was triturated with EtOAc/petroleum ether (1:1) and the solid was collected by filtration to provide compound Tnt4a (15.7 g, 85percent). ‘HNMR (400 MHz, DMSO) 11.9 (s, 1H), 7.95-7.98 (m, 1H), 7.06-7.11 (m, 1H), 6.84-6.89 (m, 1H)Step A - Synthesis of Intermediate Compound Int-4a To a solution of 2-amino-4-fluorobenzoic acid (15.5 g, 100 mmol) in THF (200 mL) cooled to 0 °C was added triphosgene (27.9 g, 105 mmol). After heating at 50 °C for 6 hours, the solvent was concentrated in vacuo. The crude residue was triturated with EtO Ac/petroleum ether (1 : 1) and the solid was collected by filtration to provide compound Int- 4a (15.7 g, 85percent). 1H MR (400 MHz, DMSO) δ 1 1.9 (s, 1H), 7.95-7.98 (m, 1H), 7.06-7.1 1 (m, 1H), 6.84-6.89 (m, 1H).To a solution of 2-amino-4-fluorobenzoic acid (15.5 g, 100 mmol) in THF (200 mL) cooled to 0° C. was added triphosgene (27.9 g, 105 mmol). After heating at 50° C. for 6 hours, the solvent was concentrated in vacuo. The crude residue was triturated with EtOAc/petroleum ether (1:1) and the solid was collected by filtration to provide compound Int-4a (15.7 g, 85percent). Example 4. Preparation of 3-(4-sec-butylphenyl)-7-fluoro-2-(4-(2-hydroxyethoxy)- 3, 5-dimethylphenyl)quinazolin-4(3H)-one (Q); [0149] To a stirred solution of 2-amino-4-fluoro benzoic acid (L) (1.15 g, 7.40 mmol) in anhydrous acetonitrile (8 ml_) at 55°C were simultaneously added anhydrous pyridine (1.2 ml_, 15 mmol) and a solution of triphosgene (0.73 g, 2.5 mmol) in anhydrous CHA. 2-Amino-4-fluorobenzoic acid methyl ester. 2-Amino-4-fluorobenzoic acid (5.0 g, 32 mmol) was dissolved in DCM (50 mL) and cooled to 0° C. Hunig's base (11 ml, 64 mmol) was added followed by triphosgene (3.8 g, 13 mmol). The reaction mixture was stirred for 5 min then allowed to warm to ambient temperature over 45 min. Water was added to the mixture, which was then extracted with DCM (3.x.), and the combined organic layers were dried (MgSO4). Filtration and concentration provided 7-fluoro-1H-benzo[d][1, 3]oxazine-2, 4-dione as a tan solid (3.94 g, 21.8 mmol, 68percent), which was taken on directly to the next step. To a solution of 7-fluoro-1H-benzo[d][1, 3]oxazine-2, 4-dione (3.94 g, 21.8 mmol) in DMF (20 mL) was added dry methanol (8.8 mL, 220 mmol) and DMAP (0.27 g, 2.2 mmol). The mixture was allowed to stand overnight, and was then partitioned between EtOAc and water. The organic layer was washed with water (3.x.) and dried (MgSO4). Filtration and purification on silica gel (MPLC, hexanes/EtOAc) provided the title methyl ester as a white solid (1.89 g, 11.1 mmol, 51percent). HPLC (reversed-phase): RT=8.66 min). 1H NMR (400 MHz, CDCl3): 7.87 (m, 1H), 6.37 (m, 2H), 3.86 (s, 3H).Bis(trichloromethyl) carbonate (3.73 g, 12.57 mmol) was added to a solution of 2- amino-4-fluorobenzoic acid (1.3 g, 8.38 mmol) in sodium hydroxide (2N in water) (8.80 mL, 17.60 mmol) and water (9 mL) at room temperature. The resulting suspension was stirred for 15 minutes then toluene (9.00 mL) was added. The mixture was stirred at room temperature for 18 hours. The resulting precipitate was collected by filtration, washed with water, followed by 20percent acetronitrile in EtAnhydrous pyridine (2 eq) was added to a solution of 2-aminobenzoic acid derivative (IA) (1 eq) in dry methylene chloride and acetonitrile (1: 1, 40 mL/g OF 2- aminobenzoic acid) at room temperature. Solid triphosgene (1/3 eq) was then added in one portion and the resulting mixture was heated at 50 °C for 2 h. The resulting solid was collected by filtration and dried in vacuo. The crude isatoic anhydrides (IIA) were typically obtained in 50-80percent yields. Though contaminated with some pyridinium hydrochloride, the anhydrides were used in the next step without further purificationA mixture of

Molecular Weight:181.12
XLogP3:1.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Exact Mass:181.01752115
Monoisotopic Mass:181.01752115
Topological Polar Surface Area:55.4
Heavy Atom Count:13
Complexity:256
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes