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

23.3 g (88.7 mmol) 5-Amino-1-(3-chloro-4,5,6,7-tetrahydropyrazolo[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.

1. concentrationThe reaction solution was concentrated
2. additiontreated
3. temperatureThe mixture was heated
4. temperatureto reflux until no more gas evolution
5. concentrationThen the mixture was concentrated
6. additionthe residue carefully added to ice-water
7. extractionThe mixture was extracted 3 times with methylene chloride
8. customthe extracts dried
9. concentrationThe organic phase was concentrated
10. temperaturethe mixture heated at 70° C. for 3 hours
11. extractionthe mixture extracted 3 times with ethyl acetate
12. customThe organic phase was separated
13. customdried
14. concentrationconcentrated
15. customThe residue was recrystallised from ethyl acetate

ORD record

ord-cf7771cf9f0c4839a548a5b1a0ed967f

Source dataset

uspto-grants-1996_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05580986