Method for the manufacture of anagrelide
AssigneeShire US Inc.
InventorsPhilip C. Lang, Roxanne P. Spencer, Wen-Lung Yeh, Michael Joseph Roth
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Abstract
Methods are provided for making Anagrelide base from 2,3-dichlorobenzaldehyde. A method is also provided for making an intermediate compound ethyl N-(2,3-dichloro-6-nitrobenzyl)glycine from 2,3-dichlorobenzaldehyde and for reducing the glycine compound using either SnCl2 or a specially defined catalyst. A cyclization method to form Anagrelide base from the corresponding iminoquinazoline compound is further provided.
Claims2
A method for making Anagrelide base 6,7-dichloro-1,5-dihydroimidazo[2,1-b]quinazoline-2(3H)one (compound III) from 2,3-dichlorobenzaldehyde (compound IX) comprising the steps:
- (a) nitrating a compound IX of the formula:
- to form compound X of the formula:
- (b) reacting compound X under reducing conditions to form compound XI of the formula:
- (c) reacting compound XI under chlorination conditions to form compound VIII of the formula:
- (d) reacting compound VIII under alkylation conditions to form compound VI of the formula:
- (e) reacting compound VI under reducing conditions to form compound I of the formula:
- (f) reacting compound I under bromocyanation conditions to form compound II of the formula:
- (g) reacting compound II under cycloalkylation conditions to form compound III of the formula:
A method for the cyclization of 5,6-dichloro-3,4-dihydro-2(1H)iminoquinazoline-3-acetate HBR (compound II) to form 6,7-dichloro-1,5-dihydroimidazo[2,1-b]quinazolin-2(3H)-one (compound III) comprising the steps of:
- suspending the iminoquinazoline salt in water;
- adding an organic base to the suspension and mixing;
- and
- separating and drying the solids to form 6,7-dichloro-1,5-dihydroimidazo[2,1-b]quinazolin-2(3H)-one.
Dependencies are inferred from the claim text.