2-BroMo-5-(chloroMethyl)pyridine hydrochloride

Synthesis of 2-bromo-5-(chloromethyl)pyridine hydrochloride (264): (6- Bromopyridin-3-yl)methanol (1) (1.0 g, 5.3 mmol) was dissolved in CHSynthesis of 2-bromo-5-((4, 4-difluoropiperidin-l-yl)methyI)pyridine (264): 2- Bromo-5-(chloromethyl)pyridine hydrochloride (263) (1.3 g, 5.2 mmol), 4, 4-difluoro piperidine (692 mg, 5.7 mmol), K2C03 (3.6 g, 26 mmol) and KI (86 mg, 0.52 mol) were added in CH3CN (15 mL). The reaction mixture was heated at 45 C for 6 h. LC-MS analysis showed the completion of reaction. After cooling down to room temperature, the reaction mixture was diluted EtOAc (100 mL), washed with H20 (100 mL), brine, dried over anhydrous Na2S04, concentrated under reduced pressure to give 2-bromo-5-((4, 4- difluoropiperidin-l -yl) methyl)pyridine (264) as white solid, which was used in next step without further purification (1.3 g, 85% yield). LCMS: m/z 291 .1 [M+H]+; = 1.77 min.Example 18; 4-{1-[(6-bromopyridin-3-yl)methyl]-3, 5-dimethyl-1H-pyrazol-4-yl}-2-chlorobenzonitrile 2-Chloro-4-(3, 5-dimethyl-1H-pyrazol-4-yl)benzonitrile (1.24 g) synthesized in Reference Example 4 and Step 2A mixture of 2-bromo-5- (chloromethyl) pyridine hydrochloride (2.00 g) obtained in step 1, acetylacetone (2.54 mL) , sodium ethoxide (2.24 g) , sodium iodide (1.23 g) and ethanol (20.0 mL) was heated at 500C for 17 hr. The reaction mixture was allowed to cool and concentrated under reduced pressure. The residue was neutralized with 0.1 mol/L hydrochloric acid and extracted twice with ethyl acetate. The organic layers were combined, washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. The obtained residue was purified by column chromatography (hexane-ethyl acetate) to give 3- [ (6-bromopyridin-3- yl) methyl] pentane-2, 4-dione (1.72 g) as a pale-yellow oilSynthesis of Reference Example 16; Step 1A solution of (beta-bromopyridin-3-yl) methanol (2.39 g) described in a reference (Ellingboe, J. W. et al. J. Med. Cheralpha. 1994, 37, 542-550.) in THF (65 mL) was ice-cooled, thionyl chloride (4.64 mL) was added, and the mixture was stirred at 0C for 6 hr. The reaction mixture was concentrated under reduced pressure. Toluene was added and the mixture was concentrated again, and dried under reduced pressure to give 2-bromo-5- (chloromethyl) pyridine hydrochloride (2.54 g) as a brown solid.

Molecular Weight:242.93
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:1
Exact Mass:240.90607
Monoisotopic Mass:240.90607
Topological Polar Surface Area:12.9
Heavy Atom Count:10
Complexity:89.1
Covalently-Bonded Unit Count:2
Compound Is Canonicalized:Yes