| abstract |
The present invention relates to a synthetic method of ruxolitinib intermediate. First, 3-cyclopentyl-3-oxopropionitrile is prepared by catalytic reaction of methyl cyclopentanecarboxylate and acetonitrile, and then 3-cyclopentyl-3 -Oxopropionitrile undergoes enzyme-catalyzed asymmetric reduction to generate chiral alcohol (S)-3-cyclopentyl-3-hydroxypropionitrile; (S)-3-cyclopentyl-3-hydroxypropionitrile is then reacted by Mitsunobu Coupled with 4-bromopyrazole to obtain ruxolitinib intermediate (3 R )-3-(4-bromo-1H-pyrazol-1-yl)-3-cyclopentanepropanecyanide; the synthesis method has The route is short, the cost is low, the conditions are mild, the stereoselectivity is good, and the advantages are suitable for large-scale industrial production. |