Imiquimod Production Process
AssigneeChemagis Ltd.
InventorsVladimir Naddaka, Eyal Klopfer, Shady Saeed, Stephen Cherkez, Oded Arad
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Abstract
Provided is a process for producing highly pure 4-amino-1-isobutyl-1H-imidazo[4,5-c]quinoline (imiquimod), which includes reacting 4-chloro-1-isobutyl-1H-imidazo[4,5-c]quinoline with a non-gaseous amine precursor. Also provided are methods for isolating highly pure imiquimod. Further provided are intermediates useful in the production of imiquimod, methods for producing such intermediates, and methods for obtaining imiquimod from such intermediates.
Claims34
A process for preparing 4-amino-1-isobutyl-1H-imidazo[4,5-c]quinoline (imiquimod) of formula (I), the process comprising:
- reacting 4-chloro-1-isobutyl-1H-imidazo[4,5-c]-quinoline of formula (II) in an organic solvent and in the presence of non-gaseous amine precursor;
- isolating the compound of formula (I);
- and
- optionally purifying the obtained compound of formula (I),
- wherein the amine precursor is guanidine or a salt thereof, urea, melamine, a semicarbazide or a salt thereof, a carbamate, 3-amino-1,2,4-triazine, 3-amino-1,2,4-triazole, or 4-amino-1,2,4-triazole.
1-isobutyl-1H-imidazo[4,5-c]quinolin-4-guanidine, of the formula (III).
A process for preparing a compound of the formula (III), the process comprising:
- reacting a compound of the formula (II) with guanidine carbonate in an organic solvent at a temperature of from about 130° C. to about 135° C.;
- adding a base to the reaction mixture;
- and
- optionally isolating the product.
A process for preparing imiquimod, the process comprising:
- hydrolyzing 1-isobutyl-1H-imidazo[4,5-c]quinolin-4-guanidine of formula (III) at a temperature of at least about 140° C. to produce imiquimod;
- cooling the reaction mixture to precipitate crude imiquimod;
- optionally isolating the crude imiquimod;
- and
- optionally purifying the crude Imiquimod.
Dependencies are inferred from the claim text.