2-Fluoro-5-bromo-3-methylpyridine

Light yellow powder

5-Bromo-2-fluoro-3-methyl pyridine STR7 To a solution of HF/pyridine (50 g) at -5 C. in a plastic beaker equipped with a magnetic stirrer was added 2-amino-5-bromo-3-methyl pyridine (7.55 g, 40.3 mmol) over a ten minute period. Sodium nitrite (3.06 g, 44.4 mmol) was added over a 15 minute period to this reaction mixture, maintaining the temperature below 10 C. After stirring for one hour, the reaction mixture was poured into ice (100 g). The solid obtained was filtered and washed with cold water. The dried solid was dissolved in dichloromethane, dried (anhydrous Na2 SO4), filtered and concentrated in vacuo to give 5-bromo-2-fluoro-3-methyl pyridine (7.2 g) as an off-white solid. M.P. 64-65 C.A MW vial was charged with General procedure: Into a 25 mL single-necked roundbottomflask were successively added 5-bromo-2, 3-difluoropyridine (0.30 g, 1.5 mmol), DMF (4 mL)and cyclopropanol (0.13 g, 2.3 mmol) under nitrogen protection. Subsequently, Cs2CO3 (0.73 g, 2.3mmol) was put into the flask at nitrogen atmosphere. After that, the mixture was heated to 50 Cand stirred at 50 C for 5 h. After completion of the reaction, the resulting mixture was diluted withH2O (30 mL) and extracted with MTBE (10 mL×3). Then the combined organic phase was washedwith saturated aqueous NaCl (10 mL×3) and dried over Na2SO4 for 0.5 h. After that, the organicphase was concentrated under reduced pressure to give crude product. The crude product waspurified by silica gel column chromatography (eluent: petroleum ether) to give desired product alight yellow liquid 68.1% yield (0.24g).General procedure: Into a 25 mL single-necked roundbottomflask were successively added 5-bromo-2, 3-difluoropyridine (0.30 g, 1.5 mmol), DMF (4 mL)and cyclopropanol (0.13 g, 2.3 mmol) under nitrogen protection. Subsequently, Cs2CO3 (0.73 g, 2.3mmol) was put into the flask at nitrogen atmosphere. After that, the mixture was heated to 50 Cand stirred at 50 C for 5 h. After completion of the reaction, the resulting mixture was diluted withH2O (30 mL) and extracted with MTBE (10 mL×3). Then the combined organic phase was washedwith saturated aqueous NaCl (10 mL×3) and dried over Na2SO4 for 0.5 h. After that, the organicphase was concentrated under reduced pressure to give crude product. The crude product waspurified by silica gel column chromatography (eluent: petroleum ether) to give desired product alight yellow liquid 68.1% yield (0.24g).Procedure C: A solution of Procedure A: A solution of Azetidin-3-ol hydrochloride 1.2 g (11 mmol) and cesium carbonate 5.1 g (16 mmol) were added to a DMF (10 mL) solution of Example 8 6-Fluoro-5-methyl-3-pyridinemethanol: alpha-(1, 1-dimethylethyl)-, 5-Bromo-2-fluoro-3-methylpyridine (2.0 g, 0.011 mol) was dissolved with stirring in anhydrous ether (30 mL) and cooled to -70 C. This was treated at 32. Reaction of cyclobutanol with sodium hydride and 5-bromo-2-fluoro-3- methylpyridine afforded the requisite 5-bromo-2-(cyclobutyloxy)-3-methylpyridine.5-Bromo-3-methyl-2-(methylthio)pyridine (B23.1) (0424) A mixture of A mixture of 5-bro mo-2- fluoro-3-methylpyridine (1 g, 5.26 mmol), CH3SNa (479 mg, 6.84 mmol) in DMF (10 mL) was stirred for 3.5 h at 0 C under N2. The mixture was diluted with 50 mL water, extracted with ethyl acetate (50 mL x 3). The combined organic layers were successively washed with 50 mL water and 50 mL brine, dried over Na2SO4, concentrated to give the title compound (1.1 g, 95%) as a white solid. LC-MS: [M+H] = 218.

Molecular Weight:190.01
XLogP3:2.3
Hydrogen Bond Acceptor Count:2
Exact Mass:188.95894
Monoisotopic Mass:188.95894
Topological Polar Surface Area:12.9
Heavy Atom Count:9
Complexity:99.1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes