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US 9,617,241 B2Granted
Intermediate compounds and process for the preparation of efinaconazole
AssigneeMapi Pharma Ltd.
InventorsAnna Gopin, Shai Rubnov, Galina Zats, Ehud Marom
Life of this patent
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Abstract
The present invention relates to a process for the preparation of (2R,3R)-2-(2,4-difluorophenyl)-3-(4-methylene-1-piperidinyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanol (Efinaconazole) and intermediates used in such process.
Claims19
A process for the preparation of Efinaconazole of formula (1), comprising the steps of:
- a) reacting a compound of formula (2) with an organometallic alkylating agent capable of introducing an ethyl group, to form an alcohol of formula (3):
- wherein X is a leaving group;
- b) converting compound (3) to an alkene of formula (4):
- c) reacting alkene (4) with 1,2,4-triazole, to form 1-(2-(2,4-difluorophenyl)but-2-en-1-yl)-1H-1,2,4-triazole (5):
- d) epoxidation of triazole-containing alkene (5), to form 1-((2-(2,4-difluorophenyl)-3-methyloxiran-2-yl)methyl)-1H-1,2,4-triazole (6);
- e) reacting epoxide (6) with 4-methylenepiperidine to form Efinaconazole of formula (1)
3 more elements
A compound represented by the structure of formula (3):
- wherein X is a leaving group selected from the group consisting of Cl, Br, I, mesylate (OMs), triflate (OTr) and tosylate (OTs).
A compound represented by the structure of formula (4);
- including (Z)- or (E)-isomers or mixtures thereof,
- wherein X is a leaving group selected from the group consisting of Cl, Br, I, mesylate (OMs), triflate (OTr) and tosylate (OTs).
Dependencies are inferred from the claim text.