Process for the preparation of (1S,4R)-cis-4-[2-amino-6-chloro-9H-purin-9-yl]-2-cyclopentene-1-methanol
The present invention relates to a process for preparing a chloropurine compound of formula (I)
1. A process for preparing a chloropurine compound of formula (I)
which comprises ring closure of a compound of formula (VII)
in the presence of a catalytic amount of acid and at least one equivalent of a trialkylorthoformate.
2. A process according to claim 1 wherein the acid is sulfuric acid, hydrochloric acid, or an alkyl or arylsulfonic acid.
3. A process according to claim 1 wherein the acid is present in an amount of from 0.05 to 0.1 equivalents by mole based on an amount of the compound of formula (VII).
4. A process according to claim 1 wherein the trialkylorthoformate is triethylorthoformate.
5. A process according claim 1 wherein the trialkylorthoformate is present in an amount of 1 to 1.5 equivalents by mole based on the amount of the compound of formula (VII).
6. A process according to claim 1 wherein the compound of formula (VII) is prepared by condensing an amino alcohol of formula (IV)
with a compound of formula (VIII)
in the presence of a base.
7. A process according to claim 6 wherein the condensation reaction is carried out in n-butanol in the presence of sodium bicarbonate.
8. A process according to claim 1 wherein the condensation reaction is carried out in n-butanol in the presence of anhydrous potassium carbonate.
9. A process according to claim 1 wherein the chloropurine compound of formula (I) prepared by the ring closure reaction is converted in situ to abacavir.