Certain chemical entities, compositions and methods

Abstract

Chemical entities that modulate PI3 kinase activity, pharmaceutical compositions containing the chemical entities, and methods of using these chemical entities for treating diseases and conditions associated with PI3 kinase activity are described herein.

1 - 22 . (canceled) 
     
     
         23 . A process for preparing a compound of formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein
 R 3  is halo; 
 
       comprising deprotecting a compound of formula: 
       
         
           
           
               
               
           
         
       
       wherein the deprotection occurs in the presence of an acid. 
     
     
         24 . The process of  claim 23 , wherein the acid is HCl. 
     
     
         25 . The process of  claim 23 , wherein the compound of formula: 
       
         
           
           
               
               
           
         
       
       is prepared by a process comprising reacting a compound of formula: 
       
         
           
           
               
               
           
         
       
       with a compound of formula: 
       
         
           
           
               
               
           
         
       
     
     
         26 . The process of  claim 25 , wherein the reaction occurs in the presence of N,N-diisopropylethylamine and n-butanol. 
     
     
         27 . The process of  claim 25 , wherein the compound of formula: 
       
         
           
           
               
               
           
         
       
       is prepared by a process comprising an intramolecular ring closure of a compound of formula: 
       
         
           
           
               
               
           
         
       
     
     
         28 . The process of  claim 27 , wherein the intramolecular ring closure occurs in the presence of hydrochloric acid and methanol. 
     
     
         29 . The process of  claim 27 , wherein the compound of formula: 
       
         
           
           
               
               
           
         
       
       is prepared by a process comprising reacting a compound of formula: 
       
         
           
           
               
               
           
         
       
       with a compound of formula: 
       
         
           
           
               
               
           
         
       
     
     
         30 . The process of  claim 29 , wherein the reaction occurs in the presence of hexamethylphosphoramide and n-butyllithium. 
     
     
         31 . The process of  claim 29 , wherein the compound of formula: 
       
         
           
           
               
               
           
         
       
       is prepared by a process comprising reacting a compound of formula: 
       
         
           
           
               
               
           
         
       
       with N,O-dimethylhydroxylamine hydrochloride. 
     
     
         32 . The process of  claim 31 , wherein the reaction occurs in the presence of triethylamine, hydroxybenzotriazole, and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide. 
     
     
         33 . The process of  claim 31 , wherein the compound of formula: 
       
         
           
           
               
               
           
         
       
       is prepared by a process comprising reacting a compound of formula: 
       
         
           
           
               
               
           
         
       
       with a compound of formula: 
       
         
           
           
               
               
           
         
       
     
     
         34 . The process of  claim 33 , wherein the reaction occurs in the presence of hexamethylphosphoramide and n-butyllithium. 
     
     
         35 . The process of  claim 33 , wherein the compound of formula: 
       
         
           
           
               
               
           
         
       
       is prepared by a process comprising reacting a compound of formula: 
       
         
           
           
               
               
           
         
       
       with di-tert-butyl dicarbonate. 
     
     
         36 . The process of  claim 35 , wherein the reaction occurs in the presence of NaHCO 3 . 
     
     
         37 . The process of  claim 35 , wherein the compound of formula: 
       
         
           
           
               
               
           
         
       
       is prepared by a process comprising reacting a compound of formula: 
       
         
           
           
               
               
           
         
       
       with methanol. 
     
     
         38 . The process of  claim 37 , wherein the reaction occurs in the presence of thionyl chloride. 
     
     
         39 . The process of  claim 23 , wherein R 3  is Cl. 
     
     
         40 . A compound of Formula V-A2: 
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salt thereof, wherein
 B is a moiety of Formula II: 
 
       
         
           
           
               
               
           
         
       
       wherein W c  is aryl, heteroaryl, heterocycloalkyl, or cycloalkyl;
 q is an integer of 0, 1, 2, 3, or 4; 
 R 1  is hydrogen, alkyl, alkenyl, alkynyl, alkoxy, amido, alkoxycarbonyl, sulfonamido, halo, cyano, or nitro; 
 R 2  is alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, heteroarylalkyl, alkoxy, amino, halo, cyano, hydroxy or nitro; 
 R 3  is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, alkoxy, amido, amino, acyl, acyloxy, alkoxycarbonyl, sulfonamido, halo, cyano, hydroxy, nitro, aryl or heteroaryl; and 
 each instance of R 9  is independently hydrogen, alkyl, or heterocycloalkyl. 
 
     
     
         41 . A method of treating a disease or disorder associated with a phosphatidyl inositol-3 kinase (PI3 kinase) in a subject having the disease or disorder, comprising administering to the subject an effective amount of a compound of  claim 40 .