5-Fluoroisatonicanhydride

Dark yellow Solid

Preparation of Compound 1. STR4 Example 9. Preparation of 3-(4-sec-butylphenyl)-6-fluoro-2-(4-(2-hydroxyethoxy)- 3, 5-dimethylphenyl)quinazolin-4(3H)-one; [0166] To a solution of 2-amino-5-fluorobenzoic acid (1.00 g, 6.40 mmol) in acetonitrile (8 mL) was added a solution of triphosgene (0.64 g, 2.1 mmol) in dichloromethane (5 mL) and pyridine (1.1 mL, 13.0 mmol) simultaneously within 5 min. The resulting pale yellow suspension was heated at 55°C for 2 hours. The solvents were evaporated under vacuum, and the residue was stirred with water (5 ml_). The precipitate obtained was filtered and dried to afford δ-fluoro-IH-benzotcdti .Sloxazine^-dione. Yield: 1.06 g (91 percent).[0167] To a suspension 6-fluoro-1 H-benzo[d][1 , 3]oxazine-2, 4-dione (1.06 g, 5.90 mmol) in DMF (5 ml_) was added 4-sec-butylphenylamine (1.95 ml_, 11.8 mmol) at room temperature. The suspension was heated at 70A solution of 5-fluoroanthranilic acid (10 g, 64.46 mmol; Aesar, Fluorochem, ABCR Product List, Eur. Pat. Appl. No. EP 647 614, Apr. 12, 1995, the contents of which are hereby incorporated by reference in their entirety) in anhydrous tetrahydrofuran (200 ml) was treated with triphosgene (12.5 g, 42.158 mmol) and stirred at 50° C. overnight. The yellow solution was cooled down to 0° C., saturated sodium hydrogen carbonate solution was added to pH 7-8, and the mixture was extracted with ethyl acetate (150 ml.x.2).The combined organic layers were dried on anhydrous sodium sulfate, ethyl acetate was evaporated, and the residue was triturated with diethyl ether. The suspension was cooled down for 30 min, the precipitate was collected by filtration, washed with diethyl ether, and dried under vacuum to give intermediate 1 (11 g, 90percent), which was a white powder. Intermediate 1 was characterized by the following spectroscopic data: [000209] To a solution of 5-fluoroanthranilic acid (10.0 g, 65.5 mmol) in THF ( 143 mL) was added solid triphosgene (6.70 g, 22.6 mmol, 0.35 equiv). The reaction mixture was stirred at rt overnight and the resulting suspension was filtered and dried to afford 9.23 g (79percent) of 5- fluoroisatoic anhydride: 1H NMR (400 MHz, DMSO-dAfter dissolving 5-fluoroanthranilic acid (2.03 g, 13.09 mmol) in THF (40 mL), triphosgene (4.08 g) was added and the mixture was stirred at room temperature overnight. After completion of the reaction, the solvent was removed and the residue was dried over under reduced pressure. The residue obtained after drying under reduced pressure was washed with acetone and then with hexane, and subsequently dried under reduced pressure in a desiccator to obtain 6-fluoroisatoic anhydride. The compound was identified by LC-MS. Yield: 1.516 g (61percent), M+1 = 181.9Trichloromethyl CHLOROFORMATE (7.01 ML, 58.13 mmol) was added to a stirred solution of Compound 34 (8.2 g, 52.85 mmol) in dry dioxane at room temperature and the solution was refluxed for 4 h. The solution was cooled in an ice bath and the solids formed were filtered. The solids were washed by ether and dried under vacuum at room temperature to yield 9.1 g (96percent) of white solids. M. P. 240 C. LH NMR (DMSO-d6): d 7.19 (dd, J= 4.2, 8.9 Hz, 1H), 7.63-7. 71 (m, 1H), 11.77 (s, 1H). EIMS (NEG. MODE) M/Z 180 (M-1). Anal. (C8H4FN03) C, H, N.Trichloromethyl chloroformate (7.01 mL, 58.13 mmol) was added to a stirred solution of 2-amino-5-fluoro benzoic acid (8.2 g, 52.85 mmol) in dry dioxane at room temperature and the solution was refluxed for 4 h. Trichloromethyl chloroformate (7.01 mL, 58.13 mmol) was added to a stirred solution of Compound 34 (8.2 g, 52.85 mmol) in dry dioxane at room temperature and the solution was refluxed for 4 h.

5-Fluoroisatoic Anhydride is a versatile pharmaceutical intermediate used in the preparation of insulin secretagogues, HCV polymerase inhibitors, anxiolytic agents and other bioactive compounds.

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