Method for preparing halofuginone derivative
OwnerXiaoqi Wanginventor
Life of this patent
Estimating the term…
Abstract
A method for preparing a halofuginone derivative, in particular a method for preparing an inhibitor medicament expressed by specific I-type procollagen in the invention a condensate of formula (II) reacts for 12-35 hours in a catalytic hydrogenation solvent with the existence of Ni—B amorphous alloy catalyst, at the hydrogen pressure of 0.1-10 Mpa and at the temperature of 10-60° C., and then the catalyst is filtered, the filtrate is decompressed to recover the solvent, the pH value is regulated to obtain a crude product of formula (I), and the crude product of the formula (I) is refined to obtain a refined product of formula (I).
Claims13
A method for preparing halofuginone compounds comprising the following steps:
- (1) reacting a condensate of formula (II) for 12-35 hours in a catalytic hydrogenation solvent under 10˜60° C. and 0.1˜1.0 MPa controlled hydrogen pressure, with presence of a Ni—B non-crystalline alloy catalyst, as shown in the following reaction formula:
- wherein the Ni—B non-crystalline alloy catalyst is prepared by loading a Ni—B non-crystalline alloy on an aluminium oxide or zeolite carrier, with a load of 1.0˜20.0% as a weight percentage;
- wherein the weight ratio between the Ni—B non-crystalline alloy catalyst and the condensate (II) is 1:10˜40;
- wherein the catalytic hydrogenation solvent is a 0.1˜0.6N acidic aqueous alcohol solution containing a mass of the catalytic hydrogenation solvent being 8-20 times that of the condensate (II);
- wherein the Ni—B non-crystalline alloy catalyst is prepared as follows:
- adding a nickel salt into an aqueous solvent until the salt is dissolved;
- then adding a carrier selected from the group consisting of aluminium oxide and zeolite;
- adding a KBH4 solution drip by drip under 0˜30° C.;
- after above reaction is over, filtering the solution, washing precipitates with deionized water until pH reaches 6.5˜7.5, and finally storing treated precipitates in anhydrous ethanol for use;
- the nickel salt above is Ni(NO3)2, NiCl2 or Ni(SO4);
- (2) filtering the Ni—B non-crystalline alloy catalyst and treating yielded filtrate to obtain crude 3-[3-[(2R,3S)-3-hydroxyl-2-piperidinyl]-2-oxypropyl]-4(3H)-quinazolinone compounds (I);
- (3) through refining procedures, obtaining refined 3-[3-[(2R,3S)-3-hydroxyl-2-piperidinyl]-2-oxypropyl]-4(3H)-quinazolinone compounds (I);
- wherein the refining procedures are as follows:
- adding the crude 3-[3-[(2R,3S)-3-hydroxyl-2-piperidinyl]-2-oxypropyl]-4(3H)-quinazolinone compounds to a re-crystallizing solvent for reflux for more than 8 hours, then decolorizing it with activated carbon and crystallizing it under 0˜40° C. for 3-8 hours to obtain refined product;
- wherein the re-crystallizing solvent is a mixed solution of alcohol, water and halohydrocarbon, the amount of the mixed solution is 5-15 times of the amount of the crude 3-[3-[(2R,3S)-3-hydroxyl-2-piperidinyl]-2-oxypropyl]-4(3H)-quinazolinone derivative compounds in weight;
- wherein the ratio of the mixed solvent for the re-crystallization is:
- the mass ratio of alcohol:water:halohydrocarbon=1:0.1˜0.3:0.05˜0.2;
- wherein the alcohol used in the solvent for the re-crystallization is C1˜C4 alcohol;
- wherein the halohydrocarbon used in the solvent for the re-crystallization is dichromethane, trichloromethane, dichroethane or carbon tetrachloride.
Dependencies are inferred from the claim text.