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US 2006/0041124 A1Published application
Process for preparing pyrrolotriazine kinase inhibitors
OwnerBang-Chi Chen, Rulin Zhao +4inventors
InventorsBang-Chi Chen, Rulin Zhao, Joseph Sundeen, Katerina Leftheris, John Hynes, Stephen Wrobleski
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Abstract
An improved process for the preparation of certain pyrrolotriazine compounds is disclosed. The compounds exhibit utility as kinase inhibitors.
Claims17
1-4. (canceled)
A process for the preparation of a pyrrolotriazine carboxylic acid comprising the step of:
- (a) reacting compound II of the formula
- wherein
- R4 is hydrogen, alkyl, aryl, or heteroaryl, and
- R5 is hydrogen, alkyl, aryl, or heteroaryl,
- with compound III of the formula
- wherein
- X is a leaving group, and
- R6 is hydrogen, alkyl, aryl, or heteroaryl,
- to afford compound IV of the formula
- wherein
- R4, R5 and R6 are as defined above;
- (b) reacting compound IV with an alcohol in the presence of a coupling reagent to form an ester V of the formula
- wherein
- R is alkyl, aryl or heteroaryl, and
- R4, R5 and R6 are as defined above
- (c) reacting the ester V with a chlorinating reagent in the presence of a base to give a Compound VI of the formula
- wherein R, R4—R6 are as defined in step (b);
- (d) reacting the Compound VI with an aniline Compound VII of the formula
- wherein
- R1 and R2 are independently selected from hydrogen and alkyl, and
- R3 is attached to any available carbon atom of the phenyl ring and at each occurrence is independently selected from hydrogen, alkyl, substituted alkyl, halogen, cyano, nitro, amino, hydroxy, alkoxy, and substituted alkoxyl,
- to give compound VIII of the formula
- wherein
- R and R1—R6 are as defined above,
- n is 0, 1, 2 or 3;
- and
- (e) reacting compound VIII with an amine NHR7R8 to afford pyrrolotriazine carboxamides and benzamides compounds of the formula
- wherein R1—R6 and n are as defined above, and
- R7 and R8 are
- (i) independently selected from hydrogen, alkyl or substituted alkyl, alkenyl or substituted alkenyl, cycloalkyl or substituted cycloalkyl, aryl or substituted aryl, heteroaryl or substituted heteroaryl, and heterocyclic or substituted heterocyclic;
- or
- (ii) R7 and R8 can be taken together with the nitrogen atom to which they are attached to form a heterocyclic or substituted heterocyclic group or a heteroaryl or substituted heteroaryl group;
- said group formed optionally containing an additional 1 or 2 heteroatoms.
30 more elements
Dependencies are inferred from the claim text.