3-Fluoro-2-pyridinemethanol

Preparation 59; (3-Fluoro-pyridin-2-yl)-methanolDissolve (6-bromo-3-fluoro-pyridin-2-yl)-methanol (850 mg, 4.13 mmol) in methanol (40 mL) then purge the solution with nitrogen. Add palladium on carbon (200 mg of 5percent wet) and stir the mixture under a hydrogen atmosphere (2 balloons) for 20 h. Filter the mixture through Celite.(R). and wash the filter cake with methanol. Concentrate the filtrate under reduced pressure and dissolve the resulting residue in chloroform (150 mL). Wash the organics with saturated aqueous sodium bicarbonate (75 mL), dry over magnesium sulfate, filter, and concentrate to give 433 mg (82percent) of the title compound which is used without further purification. 2-Hydroxymethyl-3-fluoropyridine To a neat mixture of 3-(3-((6-fluoropyridin-3-yl)methyl)isoxazol-5-yl)pyridin-2 -amine (Intermediate E, 50 mg, O. l9mmol) and 3-fluoropyridin-2-yl)methanol (235mg, l.85mmol) was added potassium 2-methylpropane-2-olate (1M in THF, l.85mL, l.85mmol) and the mixture was stirred for 30min. The mixture was transferred to a silica gel samplet which was subsequently loaded on to a Biotage Snap column. The residue was purified by column chromatography (Si02, hexane/ethyl acetate). Combined fractions were concentrated under reduced pressure. Residue was dissolved in acetonitrile (5mL) and water (lOmL), frozen and lyophilized to yield 3-(3-((6-((3-fluoropyridin-2- yl)methoxy)pyridin-3-yl)methyl)isoxazol-5-yl)pyridin-2-amine (40mg, O.l lmmol, 57%) as a white solid. MS: 378.2 [M+H]+.To a solution of tert-butyl (2R, 5S)-4-(7-bromo-6-chloro-2- (chloromethyl)-8-fluoroquinazolin-4-yl)-2, 5 -dimethylpiperazine- 1 -carboxylate (500mg, 0.96 mmol), To a solution of tert-butyl 4-(7-bromo-6-chloro-2-(chloromethyl)-8-fluoroquinazolin-4- yl)piperazine-1-carboxylate (494 mg, 1 mmol), A solution of 285 mg (2.242 mmol) (3-fluoropyridin-2-yl) -methanol (CAS: 31181-79-0) in dry dichloromethane (9 ml) under an argon atmosphere in an ice water bath with 882 mg (3:36 mmol) of triphenylphosphine and 1.12 of g (3:36 mmol) of carbon tetrabromide was added.The reaction mixture was stirred for 22 hours at room temperature.The solvent was evaporated and the residue was purified by flash chromatography using a prepacked silica gel cartridge: purified (mobile phase cyclohexane-ethyl acetate, gradient 15percent to 30percent)) to give 156 mg (11percent yield, 98percent pure) of the title compound received.

Molecular Weight:127.12
XLogP3:0.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:127.043341977
Monoisotopic Mass:127.043341977
Topological Polar Surface Area:33.1
Heavy Atom Count:9
Complexity:89.1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes