PROCESSES FOR THE PREPARATION OF (3S,4R)-3-ETHYL-4-(3H-IMIDAZO[1,2-a]PYRROLO[2,3-e]-PYRAZIN-8-YL)-N-(2,2,2-TRIFLUOROETHYL)PYRROLIDINE-1-CARBOXAMIDE AND SOLID STATE FORMS THEREOF

Abstract

The present disclosure relates to processes for preparing (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-α]pyrrolo[2.3-]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide, solid state forms thereof, and corresponding pharmaceutical compositions, methods of treatment (including treatment of rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis), kits, methods of synthesis, and products-by-process.

1 - 116 . (canceled) 
     
     
         117 . A method of treating a human patient having active ankylosing spondylitis, comprising orally administering once daily to the patient a solid dosage form comprising (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide (Compound 1) in an amount sufficient to deliver to the patient 15 mg of Compound 1 free base equivalent. 
     
     
         118 . The method of  claim 117 , wherein the patient is an adult patient. 
     
     
         119 . The method of  claim 117 , wherein the patient has had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs. 
     
     
         120 . The method of  claim 117 , wherein the patient has had an inadequate response or intolerance to methotrexate. 
     
     
         121 . The method of  claim 117 , wherein the patient has had an inadequate response or intolerance to an anti-TNF biologic agent. 
     
     
         122 . A method of treating a human patient having active ankylosing spondylitis, comprising orally administering once daily to the patient a solid dosage form comprising (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide (Compound 1) in an amount sufficient to deliver to the patient 15 mg of Compound 1 free base equivalent, wherein the method results in an Assessment of SpondyloArthritis International Society 40 (ASAS40) response at 14 weeks after the first daily administration. 
     
     
         123 . The method of  claim 122 , wherein the patient is an adult patient. 
     
     
         124 . The method of  claim 122 , wherein the patient has had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs. 
     
     
         125 . The method of  claim 122 , wherein the patient has had an inadequate response or intolerance to methotrexate. 
     
     
         126 . The method of  claim 122 , wherein the patient has had an inadequate response or intolerance to an anti-TNF biologic agent. 
     
     
         127 . A method of treating a human patient suffering from active ankylosing spondylitis that is statistically significantly superior to placebo, comprising orally administering once daily to the patient a dose of upadacitinib sufficient to deliver 15 mg of upadacitinib freebase equivalent, wherein when the method is used to treat a population of human patients suffering from active psoriatic arthritis, a statistically significantly greater percentage of patients achieve an Assessment of SpondyloArthritis International Society 40 (ASAS40) response at 14 weeks from administration of the first daily dose compared to a control group of human patients treated with placebo. 
     
     
         128 . The method of  claim 127 , wherein the patient is an adult patient. 
     
     
         129 . The method of  claim 127 , wherein the patient has had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs. 
     
     
         130 . The method of  claim 127 , wherein the patient has had an inadequate response or intolerance to methotrexate. 
     
     
         131 . The method of  claim 127 , wherein the patient has had an inadequate response or intolerance to an anti-TNF biologic agent. 
     
     
         132 . The method of  claim 127 , wherein the statistically significantly greater percentage of patients achieving an ACR70 response rate has a p value of less than 0.001. 
     
     
         133 . A method of treating human patients suffering from active ankylosing spondylitis that is statistically significantly superior to placebo, comprising orally administering once daily to each of the patients a dose of upadacitinib sufficient to deliver 15 mg of upadacitinib freebase equivalent, wherein the method results in a statistically significantly greater percentage of the patients achieving an Assessment of SpondyloArthritis International Society 40 (ASAS40) response at 14 weeks from administration of the first daily dose compared to a control group of human patients treated with placebo. 
     
     
         134 . The method of  claim 133 , wherein the patients are adult patients. 
     
     
         135 . The method of  claim 133 , wherein the patients have had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs. 
     
     
         136 . The method of  claim 133 , wherein the patients have had an inadequate response or intolerance to methotrexate. 
     
     
         137 . The method of  claim 133 , wherein the patients have had an inadequate response or intolerance to an anti-TNF biologic agent. 
     
     
         138 . The method of  claim 133 , wherein the statistically significantly greater percentage of patients achieving an ACR70 response rate has a p value of less than 0.001.