5-cyano-4-(pyrrolo [2,3B] pyridine-3-yl)-pyrimidine derivatives useful as protein kinase inhibitors

• US 8,530,489 B2
• Filed: 05/22/2012
• Issued: 09/10/2013
• Est. Priority Date: 12/21/2006
• Status: Expired due to Fees

• Current Assignee: Vertex Pharmaceuticals Incorporated
• Original Assignee: Vertex Pharmaceuticals Incorporated
• Inventors: Mortimore, Michael, Young, Stephen Clinton, Everitt, Simon Robert Lorrie, Knegtel, Ronald, Pinder, Joanne Louise, Rutherford, Alistair Peter, Durrant, Steven, Brenchley, Guy, Charrier, Jean-Damien, O'Donnell, Michael
• Primary Examiner(s): Wilson, James O
• Assistant Examiner(s): Pagano, Alexander R
• Application Number:
  US13/477,663
• Publication Number:
  US 20120309963A1
• Time in Patent Office: 476 Days
• Field of Search: 544/333, 514/256
• US Class Current: 514/269
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/02 Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
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• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
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• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
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• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/00 : Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 5/14 : of the thyroid hormones, e.g. T3, T4
• CPC Class Codes: A61P 7/00 : Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07D 471/04 : Ortho-condensed systems

Abstract

The present invention relates to compounds useful as inhibitors of protein kinase. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders. The invention also provides processes for preparing compounds of the inventions.

Claims

1. A process for preparing a compound of formula I

2. The process of claim 1, wherein the palladium catalyst is bis-(tri-tert-butylphosphine)palladium(0).

3. The process of claim 1, wherein the pyrimidine is 4-chloro-2-(methylthio)pyrimidine-5-carbonitrile and the boronate ester is 5-Trifluoromethyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridine.

4. The process of claim 1, wherein the suitable solvent is dioxane and the alkali metal carbonate is potassium carbonate.

5. The process of claim 1, wherein R² is —

SCH₃, further comprising the steps of

a) oxidizing a compound of formula 26