[Br:1][C:2]1[CH:3]=[C:4](C=O)[CH:5]=[N:6][C:7]=1[CH3:8].[CH:11](OC)([O:14][CH3:15])[O:12][CH3:13].Cl>CO>[CH3:13][O:12][CH:11]([O:14][CH3:15])[C:4]1[CH:3]=[C:2]([Br:1])[C:7]([CH3:8])=[N:6][CH:5]=1In a sealed tube charged with a solution of 5-bromo-6-methyl-3-pyridinecarbaldehyde (for a synthesis see PB62797 Intermediate 69) (191 mg, 0.955 mmol) in MeOH (15 ml) was added trimethyl orthoformate (1.045 ml, 9.55 mmol) and HCl (4M solution in 1,4-dioxane, 0.573 ml, 2.292 mmol). The reaction mixture was stirred at 70° C. for 2 h 30 min. The solution was concentrated under vacuum and the residue was diluted with saturated NaHCO3 and EtOAc. The organic phase was extracted, dried over anhydrous Na2SO4 and concentrated under reduced pressure to give a pale oil. The crude was purified by flash chromatography using a 5 g Merck silica gel cartridge, and EtOAc/Hexane 1/9 as eluent to give 5-[bis(methyloxy)methyl]-3-bromo-2-methylpyridine (129.5 mg, 52%) as a yellow oil pure enough to be used in the next step.
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