ETHYL 2-AMINO-4-FLUOROBENZOATE

A. A. A. Synthesis of ethyl 2-amino-4-fluorobenzoate (0244) To a chilled solution of 2-amino-4-fluorobenzoic acid (1.57 g, 10.1 mmol) in absolute ethanol (20 mL) was added neat thionyl chloride (4.4 mL, 60 mmol). The reaction mixture was refluxed for 4 days total, with addition of more SOClA. A. A. Synthesis of ethyl 2-amino-4-fluorobenzoate (0244) To a chilled solution of 2-amino-4-fluorobenzoic acid (1.57 g, 10.1 mmol) in absolute ethanol (20 mL) was added neat thionyl chloride (4.4 mL, 60 mmol). The reaction mixture was refluxed for 4 days total, with addition of more SOClB. Synthesis of 7-fluoro-3-hydroquinazolin-4-one (0245) To a suspension of A. Synthesis of General procedure: To a solution of 3, 3'-((4-methoxybenzyl)azanediyl)dipropanenitrile (130 mg, 0.535 mmol) inxylene (0.3 mL) in a 5 mL reaction tube, the appropriate cyanamide (0.36 mmol) and tBuOK were rapidly added (20 mg, 0.18 mmol). The reaction was heated to 130 C for 2 h andfollowed by TLC using CH2Cl2/MeOH as eluant. After cooling to room temperature, thesolvent was removed and the residue was purified by flash chromatography or HPLC.Step B: To the formamide (6 mL) solution of PREPARATION 16 Ethyl 2-Amino-4-fluorobenzoate In the manner of Preparation 7, 30.79 g (0.156 mol) of 2-acetylamino-4-fluorobenzoic acid was converted into the title compound: yield 20.43 g (71%); ir (neat) 3482 cm, 3367, 2933, 2903, 2871, 1692, 1627, 1593, 1573, 1500; 1 H-NMR(CDCl3) 1.3 ppm (triplet, 3H, OCH2 CH3), 4.3 (quartet, 2H, OCH2 CH3), 5.8 (broad singlet, 2H, NH2), 6.2-6.6 (multiplet, 2H, aromatic H), 7.2-8.0 (multiplet, 1H, aromatic H).B. Synthesis of 7-fluoro-3-hydroquinazolin-4-one To a suspension of B. Synthesis of 7-fluoro-3-hydroquinazolin-4-one To a suspension of A. Synthesis of A. Synthesis of A total of 10 g of 2-amino-4-fluoro-benzoic acid was dissolved in 129 ml of ethanol, 6.45 ml of sulfuric acid was added and the mixture was heated under reflux for 11 hours. After cooling to room temperature, the solvent was evaporated to about half. Water was added and the mixture was extracted with ethyl acetate. The resulting organic layer was washed with saturated aqueous sodium hydrogencarbonate solution and brine, dried over magnesium sulfate and the solvent was evaporated. The residue was purified and separated by silica gel column chromatography (ethyl acetate:hexane = 1:5), to give 7.57 g of the title compound as a pale yellow oil.1H-NMR ( 400 MHz, CDCl3 ) d 1.38 ( 3H, t, J = 6.8 Hz ), 4.32 ( 2H, q, J = 6.8 Hz ), 5.88 ( 2H, brs ), 6.28 - 6.38 ( 2H, m ), 7.88 ( 1H, dd, J = 8.8, 6.8 Hz )

Molecular Weight:183.18
XLogP3:2.7
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:3
Exact Mass:183.06955672
Monoisotopic Mass:183.06955672
Topological Polar Surface Area:52.3
Heavy Atom Count:13
Complexity:187
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes