Amino pyrazole dihydrochloride → 2-(5-chloro-2-(1,3-dimethyl-1H-pyrazol-4-ylamino)pyridin-4-ylamino)-4-fluoro-N-methylbenzamide

Participants

Reaction Conditions

Reaction Steps

2-(2,5-dichloropyridin-4-ylamino)-4-fluoro-N-methylbenzamide (165 mg, 0.53 mmol), 1,3-dimethyl-1H-pyrazol-4-amine dihydrochloride (193 mg, 1.05 mmol), cesium carbonate (376 mg, 1.16 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (48.6 mg, 0.08 mmol) and diacetoxypalladium (9.43 mg, 0.04 mmol) were suspended in dioxane (3 mL) and sealed into a tube. The reaction was degased, purged with nitrogen and heated to 100 °C for 16 hours => _reaction not complete._ (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine), diacetoxypalladium and cesium carbonate were added. The reaction was degased, purged with nitrogen and heated to 110 °C for 4 hours => _reaction still not complete, no progress ..._ Reaction was filtered, washed with CH2Cl2 and concentrated to dryness. The reaction mixture was purified by preparative HPLC using a Waters X-Bridge reverse-phase column (5 microns silica, 30 mm diameter, 150 mm length) and decreasingly polar mixtures of water (containing 1% acetic acid) and acetonitrile as eluent. The pure fractions were combined, basified with a saturated aqueous solution of NaHCO3 and extracted with CH2Cl2. Organic layer was washed with brine, dried over MgSO4 and concentrated to dryness to afford 2-(5-chloro-2-(1,3-dimethyl-1H-pyrazol-4-ylamino)pyridin-4-ylamino)-4-fluoro- N-methylbenzamide (8.00 mg, 3.92 %) as a green dry film.

Provenance & Evidence