Process for making beta 3 agonists and intermediates

The present invention is directed to processes for preparing beta 3 agonists of Formula (I) and Formula (II) and their intermediates. The beta 3 agonists are useful in the treatment of certain disorders, including overactive bladder, urinary incontinence, and urinary urgency.

Process for making beta 3 agonists and intermediates

The present invention is directed to a process for preparing a compound of formula I-11 through multiple-step reactions.

PROCESS FOR MAKING BETA 3 AGONISTS AND INTERMEDIATES

The present invention is directed to processes for preparing beta 3 agonists of Formula (I) and Formula (II) and their intermediates. The beta 3 agonists are useful in the treatment of certain disorders, including overactive bladder, urinary incontinence, and urinary urgency. 114-. (canceled)16. The process of claim 15 , wherein Ris selected from the group consisting of Calkyl claim 15 , benzyl claim 15 , and phenyl.17. The process of claim 16 , wherein Ris selected from the group consisting of methyl claim 16 , ethyl claim 16 , propyl claim 16 , butyl claim 16 , and benzyl.18. The process of claim 17 , wherein Ris methyl.19. The process of claim 15 , wherein the base is selected from the group consisting of NaOH claim 15 , LiOH claim 15 , KOH claim 15 , CsOH claim 15 , Ca(OH) claim 15 , Ba(OH) claim 15 , Mg(OH) claim 15 , KCO claim 15 , NaCO claim 15 , and CsCO.20. The process of claim 19 , wherein the base is NaOH claim 19 , LiOH claim 19 , or KOH.21. The process of claim 20 , wherein the base is NaOH.22. The process of claim 15 , wherein the hydrolysis of step (a) is carried out in the presence of a solvent.23. The process of claim 22 , wherein the solvent is selected from the group consisting of methanol claim 22 , water claim 22 , THF claim 22 , EtOH claim 22 , IPA claim 22 , α-methyl-THF claim 22 , and mixtures thereof.24. The process of claim 23 , wherein the solvent is a mixture of methanol/water claim 23 , THF/water claim 23 , EtOH/water claim 23 , IPA/water claim 23 , or α-methyl-THF/water.25. The process of claim 24 , wherein the solvent is a mixture of methanol/water.26. The process of claim 15 , wherein the hydrolysis of step (a) is carried out at 0° C. to 5° C.27. The process of claim 15 , wherein the solid of step (b) is isolated by crystallization.29. The process of claim 28 , wherein the solid of step (b) is isolated by crystallization.31. The crystalline compound of claim 30 , wherein the crystalline compound is a hydrate. This is a continuation ...

Process for Making Beta 3 Agonists and Intermediates

The present invention is directed to a process for preparing a compound of formula I-11 through multiple-step reactions: 115-. (canceled)17. The process of claim 16 , wherein in step (e) said oxidizing is carried out with an oxidizing agent in the presence of a solvent and a catalyst;{'sub': 2', '2, 'said solvent is selected from the group consisting of tetrahydrofuran (THF), methyl tert-butyl ether (MTBE), dichloromethane (CHCl), acetonitrile (MeCN), toluene and a mixture comprising two of said foregoing solvents;'}{'sub': '2', 'said oxidizing agent is selected from the group consisting of sodium hypochlorite (NaOCl), sodium chlorite (NaClO), hydrogen peroxide, pyridine sulfur trioxide, pyridinium chlorochromate (PCC), and N,N′-dicyclohexycarbodiimide (DCC); and'}said catalyst is 1-oxyl-2,2,6,6-tetramethylpiperidine (TEMPO) or a TEMPO analogue.18. The process of claim 16 , wherein said reaction between said compound I-7 and said compound A-4 in step (f) is carried out at a temperature of 20 to 40° C. and in the presence of a solvent selected from the group consisting of THF claim 16 , MTBE claim 16 , CHCl claim 16 , MeCN claim 16 , toluene and a mixture comprising two of said foregoing solvents.19. The process of claim 16 , wherein in step (g) said reducing is carried out in the presence of a catalyst and hydrogen gas; and{'sub': 2', '2, 'said catalyst is selected from the group consisting of Pd, Raney Ni, Pt, PdCl, and Pd(OH).'}20. The process of claim 16 , wherein said acid in step (h) is selected from the group consisting of HCl claim 16 , HBr claim 16 , trifluoroacetic acid (TFA) claim 16 , MeSOH claim 16 , TfOH claim 16 , HSO claim 16 , para-toluenesulfonic acid claim 16 , and RSOH claim 16 , wherein R is an alkyl claim 16 , an aryl or a substituted aryl.21. The process of claim 16 , wherein said P1 and said P2 are each independently selected from the group consisting of acyl (Ac) claim 16 , benzyl (Bn) claim 16 , t-butyloxycarbonyl (Boc) claim 16 , benzoyl ( ...

Process for Making Beta 3 Agonists and Intermediates

The present invention is directed to processes for preparing beta 3 agonists of Formula (I) and Formula (II) and their intermediates. The beta 3 agonists are useful in the treatment of certain disorders, including overactive bladder, urinary incontinence, and urinary urgency. 114-. (canceled)16. The process of wherein the solvent is selected from the group consisting of MeOH claim 15 , EtOH claim 15 , IPA claim 15 , n-PrOH claim 15 , MeCN claim 15 , DMF claim 15 , DMAc claim 15 , THF claim 15 , EtOAc claim 15 , IPAc claim 15 , and toluene.17. The process of claim 15 , wherein the acid is selected from the group consisting of HCl claim 15 , HBr claim 15 , HI claim 15 , HNO claim 15 , HSO claim 15 , HPO claim 15 , TFA claim 15 , and MeSOH.18. The process of claim 15 , further comprising adding EDCI to the mixture of compound I-11 claim 15 , compound i-30 claim 15 , and acid.21. The method of claim 20 , further comprising adjusting the pH to from 6.5 to 7.0.22. The method of claim 20 , wherein the molar ratio of the compound of formula A-4 to the compound of formula I-7 is from about 1:1 to about 1.2:1.23. The method of claim 20 , further comprising dissolving the compound of formula A-4 in a solvent to form a solution prior to the addition of the compound of formula I-7.24. The method of claim 23 , wherein the solvent is selected from THF claim 23 , MTBE claim 23 , CHCl claim 23 , MeCN claim 23 , toluene claim 23 , and a mixture thereof.25. The method of claim 23 , further comprising adding a base to the solution prior to the addition of the compound of formula I-7.26. The method of claim 25 , wherein the base is a tertiary amine.27. The method of claim 26 , wherein the base is N claim 26 ,N-diisopropylethylamine.28. The method of claim 25 , further comprising adding a salt to the solution prior to the addition of the compound of formula I-7.29. The method of claim 28 , wherein the salt is a lithium halide.30. The method of claim 29 , wherein the salt is selected from ...

PROCESS FOR MAKING BETA 3 AGONISTS AND INTERMEDIATES

The present invention is directed to a process for preparing a compound of formula I-11 through multiple-step reactions: 115.-. (canceled)17. The process of claim 16 , wherein the reducing agent of step (a) is selected from the group consisting of LiAlH claim 16 , LiBH claim 16 , NaBH—LiBr claim 16 , and DIBAL.18. The process of claim 16 , wherein in step (b) said solvent is selected from the group consisting of tetrahydrofuran (THF) claim 16 , methyl tert-butyl ether (MTBE) claim 16 , dichloromethane (CHCl) claim 16 , acetonitrile (MeCN) claim 16 , toluene and a mixture comprising two of said foregoing solvents.19. The process of claim 16 , wherein in step (b) said oxidizing agent is selected from the group consisting of sodium hypochlorite (NaOCl) claim 16 , sodium chlorite (NaClO) claim 16 , hydrogen peroxide claim 16 , pyridine sulfur trioxide claim 16 , pyridinium chlorochromate (PCC) claim 16 , and N claim 16 ,N′-dicyclohexycarbodiimide (DCC).20. The process of claim 16 , wherein in step (b) said catalyst is 1-oxyl-2 claim 16 ,2 claim 16 ,6 claim 16 ,6-tetramethylpiperidine (TEMPO) or a TEMPO analogue.21. The process of claim 16 , wherein said reaction between said compound I-7 and said compound A-4 in step (c) is carried out at a temperature of 20 to 40° C. and in the presence of a solvent selected from the group consisting of THF claim 16 , MTBE claim 16 , CHCl claim 16 , MeCN claim 16 , toluene and a mixture comprising two of said foregoing solvents.22. The process of claim 16 , wherein said catalyst in step (d) is selected from the group consisting of Pd claim 16 , Raney Ni claim 16 , Pt claim 16 , PdCl claim 16 , and Pd(OH).23. The process of claim 16 , wherein said reducing in step (d) is carried out in the presence of hydrogen gas.24. The process of claim 16 , wherein said acid in step (e) is selected from the group consisting of HCl claim 16 , HBr claim 16 , trifluoroacetic acid (TFA) claim 16 , MeSOH claim 16 , TfOH claim 16 , HSO claim 16 , para- ...

PROCESS FOR MAKING BETA 3 AGONISTS AND INTERMEDIATES

The present invention is directed to processes for preparing beta 3 agonists of Formula (I) and Formula (II) and their intermediates. The beta 3 agonists are useful in the treatment of certain disorders, including overactive bladder, urinary incontinence, and urinary urgency. 114-. (canceled)18. The process of claim 15 , wherein the coupling agent comprises EDC.19. The process of claim 15 , wherein the acid is HCl.20. The process of claim 15 , wherein the solvent is an aqueous solvent.21. The process of claim 15 , wherein the solvent is IPA.22. The process of claim 15 , wherein the process further comprises (b) adding aqueous ammonia to the reaction mixture of step (a) to form a slurry.23. The process of claim 22 , wherein the process further comprises (c) aging the slurry before filtration. This is a divisional application of U.S. application Ser. No. 15/057,427, filed on Mar. 1, 2016, which is a continuation application of U.S. application Ser. No. 14/354,158, filed on Apr. 25, 2014, which is a 371 National Stage Application of PCT/US12/61252, filed on Oct. 22, 2012, which claims priority from U.S. Provisional Application No. 61/552,195, filed on Oct. 27, 2011. Each of these applications is incorporated herein by reference in its entirety.This application is directed to synthetic processes for making beta 3 agonists of Formula (I) and Formula (II) and their intermediate compounds.Beta Adrenergic receptors (βAR) are present in detrusor smooth muscle of various species, including human, rat, guinea pig, rabbit, ferret, dog, cat, pig and non-human primate. However, pharmacological studies indicate there are marked species differences in the receptor subtypes mediating relaxation of the isolated detrusor; β1AR predominate in cats and guinea pig, β2AR predominate in rabbit, and β3AR contribute or predominate in dog, rat, ferret, pig, cynomolgus and human detrusor. Expression of βAR subtypes in the human and rat detrusor has been examined by a variety of techniques, and ...

PROCESS FOR MAKING BETA 3 AGONISTS AND INTERMEDIATES

The present invention is directed to a process for preparing a compound of formula I-11 through multiple-step reactions. 2. The process of claim 1 , wherein in step (c):{'sub': 2', '2, 'the solvent is selected from the group consisting of THF, MTBE, CHCl, MeCN, toluene and a mixture comprising two of the foregoing solvents;'}{'sub': '2', 'the oxidizing agent is selected from the group consisting of NaOCl, NaClO, hydrogen peroxide, pyridine sulfur trioxide, PCC, and DCC; and'}the catalyst is TEMPO or a TEMPO analogue.3. The process of claim 1 , wherein the reaction between I-7 and A-4 in step (d) is carried out at a temperature of about 20 to 40° C. and in the presence of a solvent selected from the group consisting of THF claim 1 , MTBE claim 1 , CHCl claim 1 , MeCN claim 1 , toluene and a mixture comprising two of the foregoing solvents.4. The process of claim 1 , wherein the catalyst used in step (e) is selected from the group consisting of Pd claim 1 , Raney Ni claim 1 , Pt claim 1 , PdCl claim 1 , and Pd(OH); and the reduction is carried out in the presence of hydrogen gas5. The process of claim 1 , wherein the acid in step (f) is selected from the group consisting of HCl claim 1 , HBr claim 1 , TFA claim 1 , MeSOH claim 1 , TfOH claim 1 , HSO claim 1 , para-toluenesulfonic acid claim 1 , and RSOH wherein R is alkyl claim 1 , aryl or substituted aryl.6. The process of claim 1 , wherein the reduction of step (g) is carried out in the presence of HMDS and the catalyst used is selected from the group consisting of Pt on alumina claim 1 , Pd on alumina claim 1 , Pd/C claim 1 , Pd(OH)—C claim 1 , Raney Ni claim 1 , Rh/C claim 1 , Rh/Al claim 1 , Pt/C claim 1 , Ru/C and PtO.8. The process of claim 7 , wherein the KRED enzyme is selected from the group consisting of a polypeptide of SEQ ID NO. 1 and a polypeptide of SEQ ID NO. 2.9. The process of claim 8 , further comprising a cofactor recycling system selected from the group consisting of a polypeptide of SEQ ID NO. 3 ...

Process for Making Beta 3 Agonists and Intermediates

The present invention is directed to processes for preparing beta 3 agonists of Formula (I) and Formula (II) and their intermediates. The beta 3 agonists are useful in the treatment of certain disorders, including overactive bladder, urinary incontinence, and urinary urgency. 2. The process of claim 1 , wherein the catalyst in step (a) is selected from the group consisting of Pd claim 1 , Raney Ni claim 1 , Pt claim 1 , PdCl claim 1 , and Pd(OH); and reduction reaction is carried out in the presence of hydrogen gas.3. The process of claim 1 , wherein the acid in step (b) is selected from the group consisting of HCl claim 1 , HBr claim 1 , TFA claim 1 , MeSOH claim 1 , TfOH claim 1 , HSO claim 1 , para-toluenesulfonic acid claim 1 , and RSOH wherein R is alkyl claim 1 , aryl or substituted aryl.4. The process of claim 1 , wherein the reduction of step (c) is carried out in the presence of HMDS and the catalyst used is selected from the group consisting of Pt on alumina claim 1 , Pd on alumina claim 1 , Pd/C claim 1 , Pd(OH)—C claim 1 , Raney Ni claim 1 , Rh/C claim 1 , Rh/Al claim 1 , Pt/C claim 1 , Ru/C and PtO.6. The process of claim 5 , wherein the compound I-7 is in a solution claim 5 , and the solution containing compound I-7 is added to a solution containing compound A-4.8. The process of claim 7 , wherein:{'sub': 2', '2, 'the solvent is selected from the group consisting of THF, MTBE, CHCl, MeCN, toluene and a mixture comprising two of the foregoing solvents;'}{'sub': '2', 'the oxidizing agent is selected from the group consisting of NaOCl, NaClO, hydrogen peroxide, pyridine sulfur trioxide, PCC, and DCC; and'}the catalyst is TEMPO or a TEMPO analogue.15. A process according to claim 11 , wherein said acid is HCl. This application is directed to synthetic processes for making beta 3 agonists of Formula (I) and Formula (II) and their intermediate compounds.Beta Adrenergic receptors (βAR) are present in detrusor smooth muscle of various species, including human, ...

Process for Making Beta 3 Agonists and Intermediates

The present invention is directed to processes for preparing beta 3 agonists of Formula (I) and Formula (II) and their intermediates. The beta 3 agonists are useful in the treatment of certain disorders, including overactive bladder, urinary incontinence, and urinary urgency. 114.-. (canceled)17. The method of claim 16 , further comprising adjusting the pH to from 6.5 to 7.0.18. The method of claim 16 , wherein the molar ratio of the compound of formula A-4 to the compound of formula I-7 is from about 1:1 to about 1.2:1.19. The method of claim 16 , further comprising dissolving the compound of formula A-4 in a solvent to form a solution prior to the addition of the compound of formula I-7.20. The method of claim 19 , wherein the solvent is selected from THF claim 19 , MTBE claim 19 , CHCl claim 19 , MeCN claim 19 , toluene claim 19 , and a mixture thereof.21. The method of claim 19 , further comprising adding a base to the solution prior to the addition of the compound of formula I-7.22. The method of claim 21 , wherein the base is a tertiary amine.23. The method of claim 22 , wherein the base is N claim 22 ,N-diisopropylethylamine.24. The method of claim 21 , further comprising adding a salt to the solution prior to the addition of the compound of formula I-7.25. The method of claim 24 , wherein the salt is a lithium halide.26. The method of claim 25 , wherein the salt is selected from lithium chloride and lithium bromide.27. The method of claim 16 , which is conducted at a temperature of from about 25° C. to about 40° C. This is a continuation application of U.S. application Ser. No. 16/590,180, filed on Oct. 1, 2019, which is a continuation of U.S. application Ser. No. 16/133,320, filed on Sep. 17, 2018, which is a continuation of U.S. application Ser. No. 15/808,740, filed on Nov. 9, 2017, which is a divisional application of U.S. application Ser. No. 15/057,427, filed on Mar. 1, 2016, which is a continuation application of U.S. application Ser. No. 14/354,158, ...

Process for Making Beta 3 Agonists and Intermediates

The present invention is directed to a process for preparing a compound of formula I-11 through multiple-step reactions:

Process for making beta 3 agonists and intermediates

The present invention is directed to processes for preparing beta 3 agonists of Formula (I) and Formula (II) and their intermediates. The beta 3 agonists are useful in the treatment of certain disorders, including overactive bladder, urinary incontinence, and urinary urgency.

Process for making beta 3 agonists and intermediates

The present invention is directed to a process for preparing a compound of formula I-11 through multiple-step reactions:

Process for making beta 3 angonists and intermediates

The present invention is directed to a process for preparing a compound of formula I-11 through multiple-step reactions:.

Process for making beta 3 angonists and intermediates