2,6-Lutidine → HCID 46700784, compound

Participants

Reaction Steps

Under an atmosphere of argon protective gas, (rac)-7-[4-cyano-2-(methylsulfonyl)phenyl]-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-5-methyl-4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidine-6-carbonitrile (600 mg, 1.2 mmol) was stirred in abs. dichloromethane (50 ml) with molecular sieve (0.5 g, 4 Å) for 15 min 3-(Trifluoromethyl)phenylboronic acid (704 mg, 3.7 mmol, 3 eq.) was added together with anhydrous copper(II) acetate (673 mg, 3.7 mmol, 3 eq.). Abs. pyridine (60 ml) and triethylamine (571 μl, 3.7 mmol, 3 eq.) were then added, and the mixture was stirred for 12 h. 2,6-Lutidine (864 μl, 7.4 mmol, 6 eq.) was then added, and the reaction mixture initially stirred under an atmosphere of dry air for 12 h and then left under an atmosphere of argon for 3 d. More 3-(trifluoromethyl)phenylboronic acid (235 mg, 1.2 mmol, 1 eq.), anhydrous copper(II) acetate (225 mg, 1.2 mmol, 1 eq.), 2,6-lutidine (432 μl, 3.7 mmol, 3 eq.) and a catalytic amount (spatula tip) of activated copper were then added, and the mixture was stirred under an atmosphere of dry air for 5 d. The reaction mixture was then concentrated to dryness, and the residue was applied to silica gel using dichloromethane (˜50 ml) to silica gel and purified by flash chromatography (silica gel; mobile phase: cyclohexane/ethyl acetate 1:2). The product was obtained as a solid (102 mg, 13.1% of theory).

Provenance & Evidence