3-Bromo-4-fluorobenzonitrile

WHITE CRYSTALLINE LOW MELTING SOLID

Tetrahydrofuran (100 ml) was added to a 250 ml reaction flask. 3-Bromo-4-fluorobenzaldehyde (10 g, 49.2 mmol) and aqueous ammonia (40 ml) were added with stirring. add elemental iodine (25 g, 98.5 mmol) in portions by cooling to 5 °C. Then, the reaction is raised to ambient temperature for 2 to 3 hours, and the reaction is completed. The reaction solution was poured into an aqueous solution of 10percent sodium sulfite (200 g), and extracted twice with methyl t-butyl ether (100 ml).Dry over anhydrous sodium sulfate, concentrate under reduced pressure, remove solvent, add n-heptane (20 ml), and then cool to 0-10 °C for 1h. Filtration and drying under reduced pressure gave 3-bromo-4-fluorobenzonitrile (9.6 g, yield: 97.5percent). The NMR spectrum of this compound was determined to be the same as the product of Example 1.EXAMPLE 79A 3-bromo-4-cyclopropylaminobenzonitrile A solution of The title compound (23 mg, 36.3 %, white solid) was obtained from [4- [1- (5-] [TRIBUTYLSTANNANYL-ISOXAZOL-3-YL)-ETHYL]-PIPERAZINE-L-CARBOXYLIC] acid ethyl ester [(109] mg, 0.2 mmol) and Pd (PPh3) 2Cl2 (2.0 mg) with E3 (1.00 equivalent), 3-Bromo-4-fluorophenylbenzonitrile (1.00 equivalent, CAS 79630-23-2), tris(dibenzylideneacetone)dipalladium(0) Pd2(dba)3 (0.04 equivalents, CAS 51364-51-3), X-Phos (0.08 equivalents, CAS 564483-18-7) and potassium acetate (KOAc, 3.0 equivalents) are stirred under nitrogen atmosphere in dry toluene at 110 C for 16 h. After cooling down to room temperature (RT) the reaction mixture is extracted with ethyl acetate/brine. The organic phases are collected, washed with brine and dried over MgS04. The organic solvent is removed, the crude product was washed with cyclohexane and recrystallized from EtOH.E2 (1 .00 equivalent), 3-Bromo-4-fluorophenylbenzonitrile (1 .00 equivalent, CAS 79630-23-2), tris(dibenzylideneacetone)dipalladium(0) Pd2(dba)3 (0.04 equivalents, CAS 51364-51 -3), X-Phos (0.08 equivalents, CAS 564483-18-7) and potassium acetate (KOAc, 3.0 equivalents) are stirred under nitrogen atmosphere in dry toluene at 1 10 C for 16 h. After cooling down to room temperature (RT) the reaction mixture is extracted with ethyl acetate/brine. The organic phases are collected, washed with brine and dried over MgS04. The organic solvent is removed, the crude product was washed with cyclohexane and recrystallized from EtOH.7.75 g (63.6 mmol) of phenylboronic acid, 10.6 g (53 mmol) of 5-bromo-2-fluorobenzonitrile, 8.43 g (77.5 mmol) of Na2CO3, 80 mL of water, 53 mL of THF, 53 mL of toluene, 0.357 g (1.59 mmol) of Pd(OAc2)4, and 0.968 g (3.18 mmol) of P(o-tolyl)3 were added to the three-neck flask and refluxed in a nitrogen atmosphere for 2 hours. (0292) After the reaction was completed, the reaction mixture was cooled to room temperature, and a solid precipitated by methanol was filtered and recovered. Then, a product was extracted therefrom by using CH2Cl2, dried by using MgSO4, filtered by using a silica gel pad, concentrated, and recrystallized by using CH2Cl2:hexane to obtain Intermediate I-4 (yield: 64%).Under an argon atmosphere, in a 500 ml, three-neck flask, 5.00 g of (2, 6-difluoropyridin-4-yl)boronic acid, 6.29 g of

Molecular Weight:200.01
XLogP3:2.4
Hydrogen Bond Acceptor Count:2
Exact Mass:198.94329
Monoisotopic Mass:198.94329
Topological Polar Surface Area:23.8
Heavy Atom Count:10
Complexity:162
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes