p-Toluenesulfonic acid → 4-methyl-2-(methylthio)-6-(1H-pyrazol-4-ylamino)-5-pyrimidinecarbonitrile

Beteiligte Stoffe

Reaktionsbedingungen

Reaktionsschritte

To a solution of 4-chloro-6-methyl-2-(methylthio)pyrimidine-5-carbonitrile (6.45 g, 32.2 mmol) and 1-(phenylsulfonyl)-1H-pyrazol-4-amine (7.2 g, 32.2 mmol) in 1,4-dioxane (150 mL) was added 4-methylbenzenesulfonic acid (3.06 g, 16.1 mmol). The reaction mixture was stirred overnight at 90° C. After cooling to room temperature, the precipitate was filtered, washed with saturated NaHCO3 solution and then water, dried and washed with petroleum and the mixture solvent (petroleum ether:ethyl acetate=4:1) successively to give 4-methyl-2-(methylthio)-6-(1H-pyrazol-4-ylamino)-5-pyrimidinecarbonitrile (intermediate 30, 3.6 g) as a pale solid. MS: M(C10H10N6S)=246.30, (M+1)+=247.1; 1HNMR (300 mHz, DMSO-d6) δ ppm 12.69 (1H, s), 9.87 (1H, s), 7.97 (1H, s), 3.33 (3H, m), 2.42 (3H, s). The organic eluents were concentrated under reduced pressure and the residue was treated with the same method above to afford 4-methyl-2-(methylthio)-6-{[1-(phenylsulfonyl)-1H-pyrazol-4-yl]amino}-5-pyrimidinecarbonitrile (intermediate 29, 4.26 g, 34.4% yield) as a yellow solid.

Herkunft & Nachweise