preparation of 3,5-dimethylpyridin-2-amine_industrial additives

preparation background and overview of 3,5-dimethylpyridin-2-amine

3,5-dimethylpyridin-2-amine can be used as a pharmaceutical synthesis intermediate.

preparation of 3,5-dimethylpyridin-2-amine

the preparation of 3,5-dimethylpyridin-2-amine is as follows:

step 1): 3,5-dimethylnitropyridine-n-(2,4,4-trimethylpentan-2-yl)pyridin-2-amine

to a solution of 3,5-pyridine n-oxide (5g, 40.6mmol) in dichloromethane (120ml), add diisopropylamine (26.6ml, 152mmol), tert-octylamine (2,4,4 -trimethylpentan-2-amine) (8.15 ml, 50.8 mmol) and bromo-tris-pyrrolidine-phosphonium hexafluorophosphate (24.61 g), 52.8 mmol). the mixture was stirred at room temperature for 18 hours under nitrogen. additional bromo-tris-pyrrolidinyl-hexafluorophosphate (24.61 g, 52.8 mmol) and diisopropylamine (26.6 ml, 152 mmol) were added and the reaction mixture was stirred for 4 days. sodium carbonate solution and dichloromethane were then added and the organic layer was separated using a phase separator cartridge. the solvent was removed in vacuo and the crude product was purified by flash silica (si) chromatography (0-25% ethyl acetate-cyclohexane gradient). the title compound (4.98g) was a yellow oil. lcms (2 min, high ph) rt 1.64 min, m/z (es+) 235 (m+h).

step 2): 3,5-dimethylpyridin-2-amine

3,5-dimethyl-n-(methoxypyridine 2,4,4-trimethylpentan-2-yl)pyridin-2-amine (6.5g, 27.7mmol) was mixed with 2, 2,2-trifluoroacetic acid (46 ml, 621 mmol) was heated to 50°c. 4.5 hours. the mixture was concentrated in vacuo and diluted with dichloromethane (10 ml) and water (10 ml). the layers were separated and the aqueous phase was neutralized to ph 7-8 using saturated bicarbonate solution. the product was then extracted with dichloromethane (3 × 10 ml) and the organics were dried using a phase separator cartridge. the solvent was evaporated in vacuo. the title compound, 3,5-dimethylpyridin-2-amine (2.99 g), was a white solid. lcms (2 min, high ph) rt 0.69 min, m/z (es+) 123 (m+h).