Processes for the preparation of dipyridamole
AssigneeGenerics [UK] Limited
InventorsDattatrey Kokane, Bindu Manojkumar, Vinayak Govind Gore
Life of this patent
Estimating the term…
Abstract
The present invention relates to the active pharmaceutical ingredient dipyridamole. In particular, it relates to efficient processes for the preparation of dipyridamole which are amenable to large scale commercial production and provide the required product with improved yield and purity. The present invention also relates to a novel crystallization method for the purification of dipyridamole.
Claims36
1-21. (canceled)
A process for the preparation of dipyridamole comprising reacting 2,6-dichloro-4,8-dipiperidino-pyrimido(5,4-d)pyrimidine with diethanolamine at a temperature below 130° C.
A process according to claim 1, wherein the reaction temperature is:
- (i) between about 100° C. and below 130° C.;
- and/or
- (ii) between about 100° C. and about 125° C.;
- and/or
- (iii) between about 110° C. and about 125° C.;
- and/or
- (iv) between about 110° C. and about 120° C.;
- and/or
- (v) between about 110° C. and about 115° C.;
- and/or
- (vi) between about 113° C. and about 115° C.
A process for the preparation of dipyridamole comprising the steps of:
- (a) providing a mixture of 2,6-dichloro-4,8-dipiperidino-pyrimido(5,4-d)pyrimidine and diethanolamine;
- (b) heating the mixture from step (a);
- (c) adding a C1-C6 alkyl alcohol to the solution from step (b);
- (d) adding a hydrocarbon solvent to the solution from step (c);
- (e) adding water to the solution from step (d);
- (f) cooling the mixture from step (e);
- and
- (g) isolating the resulting solid.
A process for the preparation of dipyridamole comprising the steps of:
- (a) providing a mixture of 2,6-dichloro-4,8-dipiperidino-pyrimido(5,4-d)pyrimidine, diethanolamine and either a polar aprotic solvent or a hydrocarbon solvent;
- (b) heating the mixture from step (a);
- (c) adding a C3-C8 alkyl ketone or C3-C8 alkyl nitrile solvent to the solution from step (b);
- (d) adding water to the solution from step (c);
- (e) cooling the mixture from step (d);
- (f) isolating the resulting 2-chloro-6-diethanolamino-4,8-dipiperidino-pyrimido(5,4-d)pyrimidine;
- (g) preferably drying the solid;
- (h) providing a mixture of 2-chloro-6-diethanolamino-4,8-dipiperidino-pyrimido(5,4-d)pyrimidine and diethanolamine;
- (i) heating the mixture from step (h);
- (j) adding a C1-C6 alkyl alcohol to the solution from step (i);
- (k) adding a hydrocarbon solvent to the solution from step (j);
- (l) adding water to the solution from step (k);
- (m) cooling the mixture from step (l);
- and
- (n) isolating the resulting solid.
A process for the purification of dipyridamole comprising the steps of:
- (a) heating a mixture of crude dipyridamole and diethanolamine to get a clear solution;
- (b) adding a C1-C6 alkyl alcohol to the solution from step (a);
- (c) adding a hydrocarbon solvent to the solution from step (b);
- (d) adding water to the solution from step (c);
- (e) cooling the mixture from step (d);
- and
- (f) isolating the resulting solid.
Dipyridamole with a chemical purity of greater than 99%.
Dipyridamole comprising less than 0.1% of one or more of impurities A to G.
Dependencies are inferred from the claim text.