4-(DIFLUOROMETHOXY)BENZYLBROMIDE

General procedure: 2, 5-Dihydroxybenzaldehyde (1.0 eq.) and cesium carbonate (1.0 eq.) were suspended in DMF and the suspension, warmed to 60 C for 15 min. After cooling down to rt, the corresponding bromide (1.1 eq.) was added in DMF (0.5 M concentration of 2, 5-dihydroxybenzaldehyde) and the reaction was stirred at rt for 2h for benzylic haloalkanes or at 60 C overnight for aliphatic haloalkanes. The solvents were evaporated and the crude dissolved in water and ethyl acetate. The aqueous phase was extracted with ethyl acetate (3x) and the combined organic layers were dried over magnesium sulfate, filtered and the solvent evaporated. The crude product was purified by flash chromatography.Example 7 (5RS)-2-[4-(Difluoromethoxy)benzyl]-5-(pyrrolidin-1-ylcarbonyl)-5, 6, 7, 8-tetrahydro[1, 2, 4]triazolo[4, 3-a]pyridin-3(2H)-one (Racemate) (5RS)-5-(Pyrrolidin-1-ylcarbonyl)-5, 6, 7, 8-tetrahydro[1, 2, 4]triazolo[4, 3-a]pyridin-3(2H)-one (racemate) (50.0 mg, 212 mumol) was dissolved in 3.0 ml of acetonitrile, then caesium carbonate (103 mg, 317 mumol) and A stock solution of 5-(lH-imidazol-2-yl)-l, 3-dimethylpyridin-2(lH)-one (for an example preparation, see Intermediate 4, 1.05 mmol, 199 mg), and sodium hydride (60% dispersion in mineral oil) (56 mg) was prepared in DMF (4.9 mL), and this was stirred for 15 min. 0.7 mL of the solution was then transferred to a 3 mL vial containing 1- (bromomethyl)-4-(difluoromethoxy)benzene (0.15 mmol) which was sealed and left to stir for 3 h at RT. Methanol (200 mu) was added to the reaction mixture, and the sample loaded directly for purification by MDAP (Method B). The solvent was removed under a stream of nitrogen to afford the title compound (27.5 mg, 0.08 mmol, 48%). LCMS (System A): tRET = 0.51 min; MH+ 346.

Molecular Weight:237.04
XLogP3:3.4
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:3
Exact Mass:235.96483
Monoisotopic Mass:235.96483
Topological Polar Surface Area:9.2
Heavy Atom Count:12
Complexity:124
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes