×

PROCESSES FOR PRODUCING DECITABINE

  • US 20100249394A1
  • Filed: 03/25/2010
  • Published: 09/30/2010
  • Est. Priority Date: 03/26/2009
  • Status: Abandoned Application
First Claim
Patent Images

1. 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.

View all claims
  • 1 Assignment
Timeline View
Assignment View
    ×
    ×