Process for the preparation of latanoprost
AssigneeFinetech Laboratories Ltd.
InventorsArie Gutman, Gennadiy Nisnevich, Marina Etinger, Igor Zaltzman, Lev Judovich, Boris Pertsikov
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Abstract
Disclosed is a novel process for the preparation of the anti-glaucoma drug Latanoprost, in good yield, in large amounts and with desired purity. Also disclosed are novel intermediates for the above process.
Claims15
A process for the preparation of Latanoprost [1]
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- which comprises deriving the compound [5]
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- to give the compound [7]
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- which is hydrogenated in the presence of catalyst to give the compound of the Formula [9]
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- which is reduced with diisobutylaluminum hydride at temperature range from −50 to +50° C. followed by hydrolysis of the obtained reaction mixture under basic conditions to give compound [11], which is converted into latanoprost [1]
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- werein one of R1 and R2 is an aryl carbonyl and the other one is selected from the group consisting of aryl carbonyl, acyl, trialkylsilyl, dialkylarylsilyl, 1-alkoxyalkyl, unsubstituted and alkyl-substituted tetrahydro-2H-pyran-2-yl and tetrahydrofuran-2-yl groups, and R3 is hydrogen when R1 is acyl and is equal to R1 when it is trialkylsilyl, dialkylarylsilyl, 1-alkoxyalkyl, unsubstituted or alkyl-substituted tetrahydro-2H-pyran-2-yl or tetrahydrofuran-2-yl groups;
- R4 is hydrogen when R2 is acyl and is equal to R2 when it is trialkylsilyl, dialkylarylsilyl, 1-alkoxyalkyl, unsubstituted or alkyl-substituted tetrahydro-2H-pyran-2-yl or tetrahydrofuran-2-yl groups.
Compound of the formula [7]:
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- werein one of R1 and R2 is an aryl carbonyl group and the other one is selected from the group consisting of aryl carbonyl, acyl, trialkylsilyl, dialkylarylsilyl, 1-alkoxyalkyl, unsubstituted and alkyl-substituted tetrahydro-2H-pyran-2-yl and tetrahydrofuran-2-yl groups.
Compound of the formula [9]:
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- werein one of R1 and R2 is an aryl carbonyl group and the other one is selected from the group consisting of aryl carbonyl, acyl, trialkylsilyl, dialkylarylsilyl, 1-alkoxyalkyl, unsubstituted and alkyl-substituted tetrahydro-2H-pyran-2-yl and tetrahydrofuran-2-yl groups.
Compound of the formula [11]:
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- werein R3 and R4 are selected from the group consisting of hydrogen, trialkylsilyl, dialkylarylsilyl, 1-alkoxyalkyl, unsubstituted and alkyl-substituted tetrahydro-2H-pyran-2-yl and tetrahydrofuran-2-yl groups, and one of the R3 and R4 is hydrogen group.
(3aR,4R,5R,6aS)-Hexahydro-5-(p-phenylbenzoyloxy)-4-[(3S)-5-phenyl-3-[(tetrahydro-2H-pyran-2-yl)oxy]-1E-pentenyl]-2H-cyclopenta[b]furan-2-one [7a]:
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- wherein PPB is p-phenylbenzoyl group and THP is tetrahydro-2H-pyran-2-yl group.
(3aR,4R,5R,6aS)-Hexahydro-5-(p-phenylbenzoyloxy)-4-[(3R)-5-phenyl-3-[(tetrahydro-2H-pyran-2-yl)oxy]pentyl]-2H-cyclopenta[b]furan-2-one [9a]:
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- wherein PPB is p-phenylbenzoyl group and THP is tetrahydro-2H-pyran-2-yl group.
(3aR,4R,5R,6aS)-Hexahydro-5-hydroxy-4-[(3R)-5-phenyl-3-[(tetrahydro-2H-pyran-2-yl)oxy]pentyl]-2H-cyclopenta[b]furan-2-ol [11a]:
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- wherein THP is tetrahydro-2H-pyran-2-yl group.
Dependencies are inferred from the claim text.