5-Bromo-4-fluoro-2-pyridinamine

To a solution of 2-amino-4-fluoropyridine (75.0 g, 0.67 mol) in dry acetonitrile (700 mL), N-bromosuccinimide (122.8 g, 0.69 mol) was added portion wise upon stirring and cooling in an ice-water bath. The reaction mixture was stirred at r.t. for 1 h. After evaporation under reduced pressure, the residue was thoroughly washed with water (3 x 300 mL), taken up by acetonitrile and evaporated under vacuum yielding the title compound as an off white solid (124 g, 97 percent).To a solution of 2-amino-4-fluoropyridine (75.0 g, 0.67 mol) in dry MeCN (700 mL), N-bromosuccinimide (122.8 g, 0.69 mol) was added portionwise upon stirring and cooling in an ice-water bath. The reaction mixture was stirred at r.t. for 1 h. After evaporation under reduced pressure, the residue was thoroughly washed with water (3 x 300 mL), taken up by MeCN and concentrated in vacuo yielding the title compound as an off white solid (124 g, 97 percent). LCMS (ESTo a solution of 2-amino-4-fluoropyridine (CAS 944401-77-8, 17.56 g, 157 mmol) in acetonitrile (234 mL) at 5 under nitrogen in a foil wrapped round bottom flask was added portionwise N-bromosuccinimide (28.4 g, 160 mmol) . Upon completion of the addition the mixture was stirred in darkness warming to ambient temperature over 1 hour. The reaction mixture was concentrated on the rotary evaporator and the residue was washed repeatedly with water (3 x 300 mL) to remove the succinimide. The resulting solid was collected by filtration and dried to constant mass affording the title compound as a light tan powder (23.1 g, 76yield)To a solution of 2-amino-4-fluoropyridine (CAS 94440 1-77-8, 17.56 g, 157 mmol) in acetonitrile (234 mL) at 5 °C under nitrogen in a foil wrapped round bottom flask was added portionwise N-bromosuccinimide (28.4 g, 160 mmol). Upon completion of the addition the mixture was stirred in darkness, warming to ambient temperature over 1 hour. The reactionmixture was concentrated on the rotary evaporator and the residue was washed repeatedly with water (3 x 300 mL) to remove the succinimide. The resulting solid was collected by filtration and dried to constant mass affording the title compound as a light tan powder (23.1 g, 76percent yield)0294] Solid NBS (78 mg, 0.43 mmol) was added to a solution of 3-fluoropyridin-2-amine HCl salt (162 mg, 0.72 mmol) in ACN (4 mL) at RT with stirring. The reaction was shielded from light and stirred under nitrogen. After 1.5 h, an additional amount of NBS (15 mg, 0.084 mmol) was added to the reaction. Checking the reaction again after 1.5 h, an additional amount of NBS (15 mg, 0.084 mmol) was added to the reaction until the starting material had been consumed by LCMS. After 1 h4-fluoropyridin-2-amine 2, 2, 2-trifluoroacetate (18g, 0.16mol) in acetonitrile (200 mL) was added portionwise NBS (28.6g, 0.16mol), the was stirred in the dark at 25 degrees for 4 hours. The solvent was removed under reduced pressure, the crude product was purified by flash column chromatography on silica gel the title compound as a white solid (15g, 49percent).In an aluminium foil-covered flask, Intermediate 51 (62.3 g, 506 mmol) was dissolved in acetonitrile (1500 mL), and NBS (86 g, 481 mmol) was added. The mixturewas stirred at ambient temperature for 2 h. The mixture was concentrated to afford a yellow solid. The crude material was dissolved in EtOAc (1000 mL), washed twice with saturated aqueous sodium bicarbonate solution, then with brine, dried with sodium sulphate, filtered and concentrated in vacuo, to afford a light brown solid (71.2 g). The crude material was crystallized from EtOAc (300 mL) and heptane (300 mL) to give the title compound (34.3 g) as brown crystals. LCMS 191(79Br)/193(81Br) [M+H], RT 0.79 minutes.INTERMEDIATE 135 -Bromo-4-fluoropyridin-2-amineIn an aluminium foil-covered flask, Intermediate 12 (62.3 g, 506 mmol) wasdissolved in acetonitrile (1500 mL), and NBS (86 g, 481 mmol) was added. The mixturewas stirred at ambient temperature for 2 h. The mixture was concentrated to afford a yellow solid. The crude material was dissolved in EtOAc (1000 mL), washed twice with saturated aqueous sodium bicarbonate solution, then with brine, dried with sodium sulphate, filtered and concentrated in vacuo, to afford a light brown solid (71.2 g). Thecrude material was crystallized from EtOAc (300 mL) and heptane (300 mL) to give the title compound (34.3 g) as brown crystals. Method B HPLC-MS m/z 191(79Br)/193(81Br) [M+H], RT 0.79 minutes.To a suspention of 4-fluoropyridin-2-amine (0.6g 4.04 mmol) in MeCN (20 mL) was added Et0273] JV-Bromosuccinimide (126 mg, 0.71 mmol) was added to a solution of4-fluoropyridin-2-amine TFA salt (162 mg, 0.72 mmol) in acetonitrile (4 mL) in an aluminum foil-wrapped flask in a darkened hood. The reaction solution was stirred at room temperature in darkness for 2 hours. After evaporation of the solvent, the crude product was purified on a silica gel column eluting with EtOAc to give 5-bromo-4- fluoropyridin-2-amine as an ivory solid (92 mg, 67percent). LC/MS (m/z): 190.9/192.9 (MH

Molecular Weight:191.00
XLogP3:1.3
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Exact Mass:189.95419
Monoisotopic Mass:189.95419
Topological Polar Surface Area:38.9
Heavy Atom Count:9
Complexity:101
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes