Potassium Carbonate → 3-(4-(Difluoromethoxy)-2-methylphenyl)-7-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2,6-dimethylpyrazolo[5,1-b]oxazole

Participants

Reaction Conditions

Reaction Steps

A solution of 4-(7-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2,6-dimethylpyrazolo[5,1-b]oxazol-3-yl)-3-methylphenol (Step 1) (100 mg, 0.296 mmol) in dry DMF (4 ml) was treated with potassium carbonate (205 mg, 1.482 mmol) and stirred under N2 for 30 mins at 50° C. Methyl 2-chloro-2,2-difluoroacetate (428 mg, 2.96 mmol) was added and the reaction was heated to 90° C. for 1.5 hrs. After cooling to RT, the mixture was partitioned between EtOAc and water. The organic portion was washed with brine, dried (MgSO4) and concentrated in vacuo to give a brown oil. Purification of the crude product by reverse phase chromatography [prep-HPLC (Waters system)] yielded the title compound (TFA salt) as a colourless oil. The salt was taken up in DCM (2 ml) and MP-carbonate resin (macroporous polystyrene anion-exchange resin) (500 mg, 2.8 mmol/g, Argonaut) was added and the contents stirred at RT for 30 mins. The resin was filtered, washed with DCM and the filtrate was concentrated in vacuo to give the title compound as the free base. LC-MS Rt 4.86 mins; MS m/z 388.2 [M+H]+; Method=10minLC_v002. 1H NMR (400 MHz, CDCl3) δ 7.4 (1H, d), 7.15 (1H, s), 7.10 (1H, d), 6.6 (1H, t), 2.40 (6H, m), 2.35 (6H, m), 2.20 (3H, s).

Provenance & Evidence