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US 5,212,293 AGranted
Process for the preparation of deoxynucleosides
AssigneeAmerican Cyanamid Company
InventorsKenneth E. Green, John L. Considine, Jr., Joseph D'Antuono, III, Thurairajah Padmanathan
Life of this patent
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Abstract
An improved process for the preparation of 2' and 3'-(halo-substituted)-2',3'-dideoxy nucleosides by reacting a protected anhydrothymidine compound with a halogenating composition containing a substituted organoaluminum compound which exhibits greater solubility in conventional solvents than AlF.sub.3.
Claims40
In a process for preparing a compound of the Formula I:
- ##STR7## wherein R.sub.1 and R.sub.2 may be the same or different and are selected from the group consisting of hydrogen, lower alkyl and halogen;
- R.sub.3 is selected from the group consisting of hydrogen and halogen;
- and X is a halogen;
- the improvement which comprises the steps of:
- (a) mixing a compound of the formula:
- ##STR8## wherein P is selected from the group consisting of hydrogen, triphenylmethyl, methoxytriphenylmethyl, acetyl, pivaloyl, methanesulfonyl or trialkylsilyl with a reagent of the formula H-X wherein X is a halogen;
- in the presence of a reagent of the formula:
- ##STR9## wherein R is selected from the group consisting of (C.sub.1 -C.sub.12) branched or unbranched alkyl, (C.sub.1 -C.sub.12) branched or unbranched alkoxy, phenyl, substituted phenyl, carboxylate, benzyl, enolate, carbonyl, b-diketonate, (C.sub.1 -C.sub.12) branched or unbranched thioalkyl, thiophenyl or substituted thiophenyl wherein the substituting moiety in the aforesaid substituted phenyl or substituted thiophenyl is selected from halogen, (C.sub.1 -C.sub.6) alkyl and alkoxy;
- K and M may be the same or different and are selected from the group consisting of R and hydrogen, in an inert organic solvent,
- (b) heating said compound and reagents at 40.degree.-115.degree. C. for about one to 24 hours to produce a compound of the formula:
- ##STR10## and, where P is other than hydrogen, (c) removing said protecting group.
8 more elements
In a process for preparing a compound of the formula II:
- ##STR11## wherein R.sub.1 and R.sub.2 may be the same or different and are selected from the group consisting of hydrogen, lower alkyl and halogen;
- R.sub.3 is selected from the group consisting of hydrogen and halogen;
- and X is a halogen;
- the improvement which comprises the steps of:
- (a) mixing a compound of the formula:
- ##STR12## wherein P is hydrogen or a protecting group selected from the group consisting of triphenylmethyl, methoxytriphenylmethyl, acetyl, pivaloyl, methanesulfonyl or trialkylsilyl with a reagent of the formula H-X wherein X is a halogen;
- in the presence of a reagent of the formula:
- ##STR13## wherein R is selected from the group consisting of (C.sub.1 -C.sub.12) branched or unbranched alkyl, (C.sub.1 -C.sub.12) branched or unbranched alkoxy, phenyl, substituted phenyl, hydrogen, carboxylate, benzyl, enolate, carbonyl, (C.sub.1 -C.sub.12) branched or unbranched thioalkyl, thiophenyl or substituted thiophenyl wherein the substituting moiety in the aforesaid substituted phenyl or substituted thiophenyl is selected from halogen, (C.sub.1 -C.sub.6) alkyl and alkoxy, K and M may be the same or different and are selected from the group consisting of R and hydrogen, in an inert organic solvent;
- (b) heating said compound and reagents at 40.degree.-115.degree. C. for about one to 24 hours to produce a compound of the formula:
- ##STR14## and, where P is other than hydrogen, (c) removing said protecting group.
7 more elements
Dependencies are inferred from the claim text.