64923-12-2

Upstream product

• 27532-96-3 glycine tert-butyl ester hydrochloride 
• 100-52-7 benzaldehyde 
• 38024-18-9 glycine tert-butyl ester, acetic acid salt 
• 6456-74-2 Glycine tert-butyl ester 

Downstream Products

• 86449-83-4 (2-Oxo-4-phenyl-azetidin-1-yl)-acetic acid tert-butyl ester 
• 123932-09-2 (3S,4R)-1-<(tert-butoxycarbonyl)methyl>-3-<(S)-4-phenyloxazolidinyl>-4-phenylazetidin-2-one 
• 123882-33-7 (3R,4S)-1-<(tert-butoxycarbonyl)methyl>-3-<(R)-4-phenyloxazolidinyl>-4-phenylazetidin-2-one 
• 130159-65-8 (2R,3R,4R,5S)-5-Phenyl-3-((3R,7aS)-2-phenyl-hexahydro-pyrrolo[1,2-c]imidazol-3-yl)-pyrrolidine-2,4-dicarboxylic acid 2-tert-butyl ester 4-methyl ester 
• 135075-68-2 (2S,3S,4S,5R)-3-((4S,5S)-1,3-Dimethyl-4,5-diphenyl-imidazolidin-2-yl)-5-phenyl-pyrrolidine-2,4-dicarboxylic acid 2-tert-butyl ester 4-methyl ester 
• 135212-35-0 (2R,3R,4R,5S)-3-((4R,5R)-1,3-Dimethyl-4,5-diphenyl-imidazolidin-2-yl)-5-phenyl-pyrrolidine-2,4-dicarboxylic acid 2-tert-butyl ester 4-methyl ester 
• 135075-66-0 (2S,3S,4S,5R)-5-Phenyl-3-((4R,5R)-1,3,4,5-tetraphenyl-imidazolidin-2-yl)-pyrrolidine-2,4-dicarboxylic acid 2-tert-butyl ester 4-methyl ester 
• 135075-66-0 (2S,3S,4S,5R)-5-Phenyl-3-((4S,5S)-1,3,4,5-tetraphenyl-imidazolidin-2-yl)-pyrrolidine-2,4-dicarboxylic acid 2-tert-butyl ester 4-methyl ester 
• 135075-66-0 (2S,3S,4S,5R)-5-Phenyl-3-((4R,5R)-1,3,4,5-tetraphenyl-imidazolidin-2-yl)-pyrrolidine-2,4-dicarboxylic acid 2-tert-butyl ester 4-methyl ester 
• 135212-33-8 (2R,3R,4R,5S)-5-Phenyl-3-((4R,5R)-1,3,4,5-tetraphenyl-imidazolidin-2-yl)-pyrrolidine-2,4-dicarboxylic acid 2-tert-butyl ester 4-methyl ester 

Relevant academic research and scientific papers

General Asymmetric Synthesis of Densely Functionalized Pyrrolidines via Endo-Selective [3+2] Cycloaddition of β-Quaternary-Substituted Nitroalkenes and Azomethine Ylides

A scalable endo-selective synthesis of 2,3,4,5-tetrasubstituted pyrrolidines via cycloaddition of nitroalkenes and azomethine ylides is reported using a P,N-type ferrocenyl ligand and [Cu(OTf)]2·C6H6. The robust method is tolerant of a wide range of functionalities, including rarely reported quaternary nitroalkene substitution and heteroaromatic and hindered ortho-substituted arenes on the azomethine ylide. Subsequent transformations highlight the utility of the method in the synthesis of densely functionalized small molecules suitable for fragment-based drug discovery and the cystic fibrosis C2-corrector clinical candidate ABBV-3221.

SUBSTITUTED PYRROLIDINES AND THEIR USE

The invention discloses compounds of Formula (I) wherein R1, R2, R3, R3A, R4, and R5 are as defined herein. The present invention relates to compounds and their use in the treatment of cystic fibrosis, methods for their production, pharmaceutical compositions comprising the same, and methods of treating cystic fibrosis by administering a compound of the invention.

Well-Designed Phosphine-Urea Ligand for Highly Diastereo- and Enantioselective 1,3-Dipolar Cycloaddition of Methacrylonitrile: A Combined Experimental and Theoretical Study

A novel chiral phosphine-urea bifunctional ligand has been developed for Cu-catalyzed asymmetric 1,3-dipolar cycloaddition of iminoesters with methacrylonitrile, a long-standing challenging substrate in asymmetric catalysis. Distortion-interaction energy analysis based on density functional theory (DFT) calculations reveals that the distortion energy plays an important role in the observed enantioselectivity, which can be attributed to the steric effect between the phosphine ligand and the dipole reactant. DFT calculations also indicate that nucleophilic addition is the enantioselectivity-determining step and hydrogen bonding between the urea moiety and methacrylonitrile assists in control of the diastereo- and enantioselectivity. By a combination of metal catalysis and organocatalysis, excellent diastereo- and enantioselectivities (up to 99:1 diastereomeric ratio, 99% enantiomeric excess) as well as good yields are achieved. A wide range of substitution patterns of both iminoester and acrylonitrile is tolerated by this catalyst system, providing access to a series of highly substituted chiral cyanopyrrolidines with up to two quaternary stereogenic centers. The synthetic utility is demonstrated by enantioselective synthesis of antitumor agent ETP69 with a pivotal nitrile pharmacophore and an all-carbon quaternary stereogenic center.

Application of the Cu(i)/TEMPO/O2 catalytic system for aerobic oxidative dehydrogenative aromatization of pyrrolidines

A Cu(i)/TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxy)-catalyzed aerobic oxidative dehydrogenative aromatization reaction of fully saturated pyrrolidines to synthesize multi-substituted pyrroles was developed for the first time. The use of a non-precious metal catalyst, green oxidant and environmentally friendly solvent made the reaction more sustainable.

Substituted Pyrrolidines and Methods of Use

The invention discloses compounds of Formula (I) wherein R1, R2, R2A, R3, R3A, R4, R4A, and R5 are as defined herein. The present invention relates to compounds and their use in the treatment of cystic fibrosis, methods for their production, pharmaceutical compositions comprising the same, and methods of treating cystic fibrosis by administering a compound of the invention.

Tandem nucleophilic addition-cycloaddition of arynes with α-iminoesters: Two concurrent pathways to imidazolidines

The tandem nucleophilic addition-cycloaddition reaction has been developed for the synthesis of functionalized imidazolidine derivatives. A variety of α-iminoesters and aryne precursors were well tolerated under the mild reaction conditions. This asymmetric cycloaddition afforded imidazolidine derivatives with high yields, complete regioselectivities, and excellent diastereo- and enantioselectivities. Aryne-induced ylides working as 1,3-dipoles for asymmetric cycloaddition are the notable feature of the present reaction. In the tandem reaction, the [3+2] cycloaddition of aryne-induced ylides with metallized α-iminoesters and metal-catalyzed [3+2] cycloaddition of azomethine ylide with α-iminoesters are two concurrent pathways to imidazolidines.

Stereoselective and Site-Specific Allylic Alkylation of Amino Acids and Small Peptides via a Pd/Cu Dual Catalysis

We report a stereoselective and site-specific allylic alkylation of Schiff base activated amino acids and small peptides via a Pd/Cu dual catalysis. A range of noncoded α,α-dialkyl α-amino acids were easily synthesized in high yields and with excellent enantioselectivities (up to >99% ee). Furthermore, a direct and highly stereoselective synthesis of small peptides with enantiopure α-alkyl or α,α-dialkyl α-amino acids residues incorporated at specific sites was accomplished using this dual catalyst system.

A rapid and divergent access to chiral azacyclic nucleoside analogues via highly enantioselective 1,3-dipolar cycloaddition of β-nucleobase substituted acrylates

A rapid and divergent access to chiral azacyclic nucleoside analogues has been established via highly exo-selective and enantioselective 1,3-dipolar cycloaddition of azomethine ylides with β-nucleobase substituted acrylates. Using 1 mol% of a chiral copper complex, various chiral azacyclic nucleoside analogues were obtained in high yields, excellent exo-selectivities and enantioselectivities (98 to >99% ee). This journal is

METHOD FOR PRODUCING OPTICALLY ACTIVE 1-AMINO-2-VINYLCYCLOPROPANECARBOXYLIC ACID ESTER

1-Amino-2-vinylcyclopropanecarboxylic acid ester, which is useful as a synthetic intermediate of pharmaceuticals, can be produced by a process of producing 1-amino-2-vinylcyclopropanecarboxylic acid ester represented by formula (4): including a step of hydrolysis of an optically active 1-N-(arylmethylene)amino-2-vinylcyclopropanecarboxylic acid ester represented by formula (3): which is obtained by reacting an N-(arylmethylene)glycine ester represented by formula (1): with a compound represented by formula (2): in the presence of a base and an optically active quaternary ammonium salt.

Diastereoselective lithium salt-assisted 1,3-dipolar cycloaddition of azomethine ylides to the fullerene C60

An efficient method for the diastereoselective synthesis of 5-substituted 3,4-fulleroproline esters based on the lithium salt-assisted cycloaddition of azomethine ylides has been developed. A series of the fulleroproline esters containing either electron donating or electron withdrawing substituents was prepared with high yields and diastereoselectivities provided by the S-trans-configuration of ylide generated in situ from the corresponding Schiff base in the presence of a lithium salt and base. This method provides easy preparation of 3,4-fulleroproline derivatives suitable for fullerene-based peptide synthesis.