Compounds for preparing pyrrole six-membered heteroaryl ring derivative

Abstract

Intermediate compounds used in the preparation of pyrrole six-membered heteroaryl ring derivatives are disclosed. In particular, compounds of formula (IB) are disclosed. The compounds of formula (IB) are used in the synthesis of Janus kinase (JAK) inhibitors. Substituents in formula (IB) have the same definitions as in the description.

What is claimed is: 
     
         1 . A compound of formula (IB), or a tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof: 
       
         
           
           
               
               
           
         
         wherein: 
         L is a bond or alkyl; 
         R 1  is selected from the group consisting of hydrogen, alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, —(CH 2 ) n C(O)OR 15 , —OC(O)R 15 , —C(O)R 15 , —C(O)NR 16 R 17 , —NHC(O)R 15 , —NR 16 R 17 , —OC(O)NR 16 R 17 , —NHC(O)NR 16 R 17 , and —S(O)mR 15 , wherein the alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl is optionally substituted with one or more groups selected from the group consisting of halogen, hydroxy, cyano, nitro, alkyl, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, —(CH 2 ) n C(O)OR 15 , —OC(O)R 15 , —C(O)R 15 , —C(O)NR 16 R 17 , —NHC(O)R 15 , —NR 16 R 17 , —OC(O)NR 16 R 17 , —NHC(O)NR 16 R 17 , —S(O) m R 15 , —NHC(O)(O)R 15 , and —NHS(O) m R 15 ; 
         R 2  is selected from the group consisting of hydrogen and alkyl; 
         R 5  and R 6  are each independently selected from the group consisting of hydrogen, alkyl, and aryl, wherein the alkyl or aryl is optionally substituted with one or more groups selected from the group consisting of alkyl and halogen; 
         each of R 7 , R 8 , R 9 , and R 10  are independently selected from the group consisting of hydrogen, alkyl, hydroxyalkyl, and halogen, 
         or R 7  and R 8  or R 9  and R 10  are taken together to form an oxo group; 
         each of R 11 , R 12 , R 13 , and R 14  is independently selected from the group consisting of hydrogen, alkyl and halogen, 
         or R 11  and R 12  or R 13  and R 14  are taken together to form an oxo group; 
         R 15  is selected from the group consisting of hydrogen, alkyl, cycloalkyl, heterocyclyl, alkenyl, alkynyl, aryl, and heteroaryl, wherein the alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl is optionally substituted with one or more groups selected from the group consisting of alkyl, halogen, hydroxy, cyano, amino, nitro, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, —(CH 2 ) n C(O)OR 18 , —OC(O)R 18 , —C(O)R 18 , —C(O)NR 19 R 20 , —NHC(O)R 18 , —NR 19 R 20 , —OC(O)NR 19 R 20 , —NHC(O)NR 19 R 20 , —S(O) m R 18 , —NHC(O)OR 18 , and —NHS(O) m R 18 ; 
         R 16  and R 17  are each independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl, wherein the alkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more groups selected from the group consisting of alkyl, halogen, hydroxy, cyano, amino, alkoxy, cycloalkyl, heterocyclyl, hydroxyalkyl, alkynyl, aryl, heteroaryl, carboxyl, alkoxycarbonyl, and —OR 18 ; 
         R 18  is selected from the group consisting of hydrogen, alkyl, cycloalkyl, heterocyclyl, hydroxyalkyl, aryl, and heteroaryl; 
         R 19  and R 20  are each independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl; 
         m is 0, 1, or 2; 
         n is 0, 1, or 2; 
         p is 0, 1, or 2; 
         q is 0, 1, or 2; 
         s is 0, 1, or 2; and 
         t is 0, 1, or 2. 
       
     
     
         2 . The compound of  claim 1 , wherein R 1  is —(CH 2 ) n C(O)OR 15 . 
     
     
         3 . The compound of  claim 1 , wherein R 2  is alkyl. 
     
     
         4 . The compound of  claim 1 , wherein s and t are both 0; and p and q are both 1. 
     
     
         5 . The compound of  claim 1 , wherein s, t, p, and q are each 1. 
     
     
         6 . The compound of  claim 1 , wherein p and q are both 1; and one of s and t is 1 and the other of s and t is 0. 
     
     
         7 . The compound of  claim 1 , wherein one of p and q is 1 and the other of p and q is 2; and one of s and t is 1 and the other of s and t is 2. 
     
     
         8 . The compound of formula (IB) of  claim 1 , wherein R 5  and R 6  are each independently selected from the group consisting of hydrogen and alkyl. 
     
     
         9 . The compound of formula (IB) of  claim 1 , wherein each of R 7  to R 14  is hydrogen. 
     
     
         10 . The compound of formula (IB) of  claim 1 , wherein n is 0; and R 15  is alkyl, wherein the alkyl is optionally substituted with aryl. 
     
     
         11 . A compound of formula (IB), or a tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof: 
       
         
           
           
               
               
           
         
         wherein 
         L is a bond or alkyl; 
         R 1  is —(CH 2 ) n C(O)OR 15 ; 
         R 2  is selected from the group consisting of hydrogen and alkyl; 
         R 5  to R 14  are each independently selected from the group consisting of hydrogen and alkyl; 
         R 15  is selected from the group consisting of hydrogen and alkyl, wherein the alkyl is optionally substituted with aryl; 
         n is 0, 1, or 2; 
         p is 0, 1, or 2; 
         q is 0, 1, or 2; 
         s is 0, 1, or 2; and 
         t is 0, 1, or 2. 
       
     
     
         12 . The compound of  claim 11 , wherein R 1  is tert-butoxycarbonyl. 
     
     
         13 . The compound of  claim 11 , wherein R 2  is methyl. 
     
     
         14 . The compound of  claim 11 , wherein s, t, p, and q are each 1. 
     
     
         15 . The compound of  claim 11 , wherein p and q are both 1; and one of s and t is 1 and the other of s and t is 0. 
     
     
         16 . The compound of  claim 11 , wherein one of p and q is 1 and the other of p and q is 2; and one of s and t is 1 and the other of s and t is 2. 
     
     
         17 . The compound of  claim 11 , wherein R 2  is methyl. 
     
     
         18 . A compound selected from the group consisting of: 
       
         
           
           
               
               
           
         
         or a tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof.