Iodoethane → 1-(3-Chloro-4,5,6,7-tetrahydropyrazolo [1,5-a]-pyridin-2-yl)-5-(ethylmethylamino)-4-pyrazolecarbonitrile

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Reaction Steps

23.3 g (88.7 mmol) 5-Amino-1-(3-chloro-4,5,6,7-tetrahydro-pyrazolo[1,5-a]pyridin-2-yl)-4-pyrazolecarbonitrile, 202 ml (1,21 mmol) triethyl orthoformate and 10 drops trifluoroacetic acid was heated for 5 hours with removal of water in a water bath at a temperature of 150° C. The reaction solution was concentrated, the residue was suspended in 250 ml ethanol and treated, portionwise, with cooling with 4.2 g (106.4 mmol) sodium borohydride. The mixture was heated to reflux until no more gas evolution was observed. Then the mixture was concentrated and the residue carefully added to ice-water. The mixture was extracted 3 times with methylene chloride and the extracts dried. The organic phase was concentrated. 2.61 g (87.1 mmol) Sodium hydride (80%) was added to 150 ml tetrahydrofuran and at 0° C., 24.1 g (87.1 mmol) of the resulting 1-(3-chloro-4,5,6,7-tetrahydropyrazolo-[1,5-a]pyridin-2-yl)-5-methylamino-4-pyrazolecarbonitrile in 500 ml tetrahydrofuran was added dropwise. After stirring for 1 hour at room temperature, 7.82 ml (95.8 mmol) iodoethane was added and the mixture heated at 70° C. for 3 hours. Water was added dropwise and the mixture extracted 3 times with ethyl acetate. The organic phase was separated, dried and concentrated. The residue was recrystallised from ethyl acetate.

Provenance & Evidence