2-Bromo-5-chloro-4-fluorobenzenamine

To a solution of Compound 56 (5g, 34.3mmol) in dichloromethane (60mL) was added pyridine (4.2ml, 51.5mmol)under ice-cooling, dropwised a solution of bromine (1.8ml, 34.3mmol) in dichloromethane (40mL), the solution wasstirred for 1 hour. To the reaction mixture was added sodium thiosulfate aqueous solution, and extracted with ethylacetate. The organic layer was dried with anhydrous sodium sulfate, and concentrated under reduced pressure. Theresidue was purified by silica gel chromatography (ethyl acetate / hexane) to yield Compound 57 (6.4g, yield: 83percent) asan orange solid.LC-MS: m/z=223. [M+H]+To a solution of 3-chloro-4-fluoroaniline (5.82 g, 0.04 mol) in CHTo a stirred solution of 3-chloro-4-fluoroaniline (Tokyo Chemical Industry, 5.00 g, 34.4 mmol) and dry pyridine (3.50 mL, 43.3 mmol) in dry CHTo a solution of Compound 56 (5g, 34.3mmol) in dichloromethane (60mL) was added pyridine (4.2ml, 51.5mmol)under ice-cooling, dropwised a solution of bromine (1.8ml, 34.3mmol) in dichloromethane (40mL), the solution wasstirred for 1 hour. To the reaction mixture was added sodium thiosulfate aqueous solution, and extracted with ethylacetate. The organic layer was dried with anhydrous sodium sulfate, and concentrated under reduced pressure. Theresidue was purified by silica gel chromatography (ethyl acetate / hexane) to yield Compound 57 (6.4g, yield: 83%) asan orange solid.LC-MS: m/z=223. [M+H]+To a solution of 3-chloro-4-fluoroaniline (5.82 g, 0.04 mol) in CH2Cl2(150 mL), N-bromosuccinimide (7.12 g, 0.04 mol) was added in portions at 0C under stirring. Upon completion of the addition, the resultant was stirred for 30 minutes and filtered. The filtrate was concentrated and purified by silica gel column chromatography to give To a stirred solution of 3-chloro-4-fluoroaniline (Tokyo Chemical Industry, 5.00 g, 34.4 mmol) and dry pyridine (3.50 mL, 43.3 mmol) in dry CH2Cl2 (17.0 mL) was added dropwise a solution of bromine (1.90 mL, 36.9 mmol) in CH2Cl2 (10.0 mL) at 0 C under N2. The reaction mixture was stirred at the temperature under N2 for 1 h, warmed up to room temperature, and stirred for 1 h. The mixture was poured into H2O and then extracted with AcOEt. The extracts were dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography (silica gel, hexane/AcOEt = 10:1) to afford 2.76 g of the title product 18 in 36% yield as a brown solid. 1H NMR (270 MHz, CDCl3) delta 7.22 (1H, d, J = 8.6 Hz), 6.77 (1H, d, J = 6.4 Hz), 3.84 (2H, br s).To a mixture of compound 72a (2.0 g, 9.0 mmol) in toluene (15 mL) was added formic acid (1.0 g, 22 mmol), the resulting mixture was refluxed for 8 hours. The mixture was concentrated in vacuum and the crude product was washed with methanol (10 mL), and then filtered. The solid was dried in vacuum to afford compound 72b (1.6 g, 71% yield) as a white solid. LCMS: Rt = 1.12 min in 3 min chromatography (3min-5-95%MeCN in water (0.02%FA), Waters Acquity UPLC BEH C18 1.7um, 2.1*50 mm, 40C), MS (ESI) m/z= 252.0, 254.0 [M+H] +.

Molecular Weight:224.46
XLogP3:2.7
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:222.91997
Monoisotopic Mass:222.91997
Topological Polar Surface Area:26
Heavy Atom Count:10
Complexity:124
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes