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US 2010/0249394 A1Published application
Processes for producing decitabine
AssigneeAlbemarle Corporation
InventorsYunqi Liu, Gregory H. Lambeth, Brian W. Nixon
Life of this patent
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Abstract
New processes for producing decitabine are provided.
Claims6
A process comprising:
- (a) combining at least 2-deoxy-D-ribose and methanol to yield a first combination, wherein the amount of methanol is at least about 4 grams per gram of the 2-deoxy-D-ribose and the methanol is substantially anhydrous;
- (b) cooling the first combination to about 25° C. to about −20° C.;
- (c) combining at least an acyl halide and at least a portion of the first combination to yield a second combination;
- (d) maintaining the second combination at about 25° C. to about −20° C. for about 30 minutes to about 240 minutes;
- (e) combining at least a first volatile tertiary amine and at least a portion of the second combination to yield a first product comprising 1-O-methyl-2-deoxy-D-ribofuranose and methanol;
- (f) removing substantially all of the methanol from the first product, yielding a substantially methanol-free first product;
- (g) combining at least a substantially anhydrous Solvent A, a Catalyst A, a second volatile tertiary amine, and at least a portion of the substantially methanol-free first product to yield a third combination;
- (h) combining at least p-chlorobenzoyl chloride and at least a portion of the third combination to yield a fourth combination;
- (i) stirring the fourth combination for about 2 hours to about 6 hours at about 10° C. to about 40° C.;
- (j) filtering the fourth combination to yield a filtrate and a filter cake;
- (k) collecting the filtrate;
- (l) rinsing the filter cake with at least a substantially anhydrous rinsing solvent;
- (m) combining at least acetic acid, at least a portion of the filtrate, and at least a portion of the used rinsing solvent to yield a fifth combination;
- (n) combining at least HCl gas and at least a portion of the fifth combination at about −10° C. to about 25° C. to yield a sixth combination;
- (o) stirring the sixth combination;
- (p) collecting a second product comprising 1-[3,5-di-O-(p-chlorobenzoyl)]-2-deoxy-alpha-D-ribofuranosyl-chloride from the sixth combination;
- (q) drying the second product to yield at least 1-[3,5-di-O-(p-chlorobenzoyl)]-2-deoxy-alpha-D-ribofuranosyl-chloride;
- (r) yielding beta:alpha anomers of 4-amino-1-[3,5-di-O-(p-chlorobenzoyl)]-2-deoxy-D-ribofuranosyl-1,3,5-triazin-2(1H)-one from at least the 1-[3,5-di-O-(p-chlorobenzoyl)]-2-deoxy-alpha-D-ribofuranosyl-chloride;
- and
- (s) yielding decitabine from at least the beta:alpha anomers of 4-amino-1-[3,5-di-O-(p-chlorobenzoyl)]-2-deoxy-D-ribofuranosyl-1,3,5-triazin-2(1H)-one.
17 more elements
A process comprising:
- (a) combining at least 1-O-methyl-3,5-di-O-p-chlorobenzoyl-2-deoxy-alpha/beta-D-ribose, acetic acid, an acyl halide, and a substantially anhydrous solvent to yield a first combination;
- (b) while stirring and in the presence of an inert gas, feeding gaseous HCl to the first combination at about −10° C. to about 25° C. to yield a second combination comprising 1-[3,5-di-O-(p-chlorobenzoyl)]-2-deoxy-alpha-D-ribofuranosyl-chloride;
- (c) stirring the second combination at about −10° C. to about 25° C.;
- (d) yielding from the second combination a product comprising 1-[3,5-di-O-(p-chlorobenzoyl)]-2-deoxy-alpha-D-ribofuranosyl-chloride;
- (e) rinsing the product with a rinse;
- (f) drying the product to yield at least 1-[3,5-di-O-(p-chlorobenzoyl)]-2-deoxy-alpha-D-ribofuranosyl-chloride;
- (g) yielding beta:alpha anomers of 4-amino-1-[3,5-di-O-(p-chlorobenzoyl)]-2-deoxy-D-ribofuranosyl-1,3,5-triazin-2(1H)-one from at least the 1-[3,5-di-O-(p-chlorobenzoyl)]-2-deoxy-alpha-D-ribofuranosyl-chloride;
- and
- (h) yielding decitabine from at least the beta:alpha anomers of 4-amino-1-[3,5-di-O-(p-chlorobenzoyl)]-2-deoxy-D-ribofuranosyl-1,3,5-triazin-2(1H)-one.
6 more elements
Dependencies are inferred from the claim text.