Aminopyrazole triazolothiadiazole inhibitor of c-Met protein kinase
AssigneeVertex Pharmaceuticals Incorporated
InventorsDavid J. Lauffer, Pan Li, Stefanie Roeper, Shereen Ibrahim, Anuj K. Kuldipkumar, Yi Shi, David B. Miller, Jr.
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Abstract
The present invention relates to anhydrous and hydrated forms of Compound 1, which are useful in the inhibition of c-Met protein kinase. The invention also provides pharmaceutically acceptable compositions comprising compounds of formula I and methods of using the compositions in the treatment of proliferative disorders.
Claims11
A compound having the formula:
- said compound being in an anhydrous form.
A compound having the formula:
- said compound being in a dihydrate form.
A method of preparing 3-(difluoro(quinolin-6-yl)methyl)-N-(heteroaryl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-6-amines, said method comprising treating sodium 2,2-difluoro-2-(quinolin-6-yl)acetate with thiocarbohydrazine in the presence of propanephosphonic acid anhydride to produce 4-amino-5-(difluoro(quinolin-6-yl)methyl)-4H-1,2,4-triazole-3-thiol;
- reacting 4-amino-5-(difluoro(quinolin-6-yl)methyl)-4H-1,2,4-triazole-3-thiol with triphenylphosphine to produce 5-(difluoro(quinolin-6-yl)methyl)-4-(iminotriphenylphosphorano)-4H-1,2,4-triazole-3-thiol;
- and reacting 5-(difluoro(quinolin-6-yl)methyl)-4-(iminotriphenylphosphorano)-4H-1,2,4-triazole-3-thiol with an isocyanto heteroaromatic compound to produce a 3-(difluoro(quinolin-6-yl)methyl)-N-(heteroaryl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-6-amine, wherein said heteroaryl group is optionally substituted with up to 3 groups selected from fluoro, chloro, —NH2, —NH(C1-4 aliphatic), —N(C1-4 aliphatic)2, C1-4 aliphatic, —OH, —O(C1-4 aliphatic), —NO2, —CN, —C(O)OH, —C(O)O(C 1-4 aliphatic), —O(C1-4 aliphatic) containing 1-3 fluorines, or C1-4 aliphatic containing 1-3 fluorine.
Dependencies are inferred from the claim text.