N-(1,3-dimethylpyrazol-4-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine → HCID 44609039, compound

Participants

Reaction Conditions

Reaction Steps

A suspension of 6-amino-4-methyl-3,4-dihydrobenzo[f][1,4]oxazepin-5(2H)-one (151 mg, 0.79 mmol), N-(1,3-dimethyl-1H-pyrazol-4-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine (150 mg, 0.39 mmol), diacetoxypalladium (4.41 mg, 0.02 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (22.71 mg, 0.04 mmol) and cesium carbonate (256 mg, 0.79 mmol) in dioxane (2 mL) was degassed with argon then stirred at 100 °C for 2 hours sealed in a microwave vial. The reaction mixture was purified by preparative HPLC using a Waters X-Bridge reverse-phase column (C-18, 5 microns silica, 19 mm diameter, 100 mm length, flow rate of 40 ml / minute) and decreasingly polar mixtures of water (containing 0.2% ammonium carbonate) and acetonitrile as eluent. The fractions containing the desired compound were evaporated to dryness to afford impure product EN01775-27-01. The impure product was repurified by flash chromatography on silica gel eluting with 0 to 5% methanol in ethyl acetate/DCM (1/1). The solvent was evaporated to dryness to afford 118mg of a sticky foam, which was triturated in a mixture of tBuOMe and pentane (~30-40% of tBuOMe). The mixture was concentrated down to get a light white foam, which could be handled.

Provenance & Evidence