Cesium carbonate → HCID 59784645, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of [4-(2-Chloro-pyrimidin-4-yl)-phenyl]-dimethyl-amine (2.0 g, 8.58 mM), 3-Amino-1H-pyrazole-4-carboxylic acid ethyl ester (1.32 g, 8.58 mM), Cs2CO3 (4.4 g, 13.58 mM) in DMF (15 ml) was heated 2 hr at 105° C. The reaction was then cooled to room temperature and diluted with water (100 mL) and the yellow precipitate collected via filtration and was washed with water (2×30 ml) then ethyl ether (2×30 ml). The solid was dried under vacuo and comprised a mixture of 3-Amino-1-[4-(4-dimethylamino-phenyl)-pyrimidin-2-yl]-1H-pyrazole-4-carboxylic acid ethyl ester and 5-Amino-1-[4-(4-dimethylamino-phenyl)-pyrimidin-2-yl]-1H-pyrazole-4-carboxylic acid ethyl ester in a ratio of approximately 6:4. The solid is flushed thru a pad of silica eluting with 5% MeOH/dichloromethane/1% TEA and the material is pooled and evaporated to a solid. Crystallization from dichloromethane/MeOH afforded the slower of the two isomers 3-Amino-1-[4-(4-dimethylamino-phenyl)-pyrimidin-2-yl]-1H-pyrazole-4-carboxylic acid ethyl ester (1.1 g, 36.4% yield) as a bright yellow solid. ES-MS MH+353, 1H NMR (300 MHz, ppm, DMSO-d6): 8.84 (s, 1H), 8.63 (d, 1H), 8.15 (d, 2H), 7.77 (d, 1H), 6.93 (d, 2H), 5.85 (br s, 2H) 4.27 (q, 2H), 3.04 (s, 6H), 1.32 (t, 3H). Chromatography of the filtrate on silica eluting 1% TEA/EtOAc can provide the other faster isomer 5-Amino-1-[4-(4-dimethylamino-phenl)-pyrimidin-2-yl]-1H-pyrazole-4-carboxylic acid ethyl ester as an off-white solid. ES-MS MH+ 353, 1H NMR (300 MHz, ppm, DMSO-d6): 8.7 (d, 1H), 8.12 (d, 2H), 7.83 (d, 1H), 7.79 (s, 1H), 7.64 (br S, 2H), 6.84 (d, 2H), 4.28 (q, 2H), 3.04 (s, 6H), 1.28 (t, 3H).

Provenance & Evidence