122079-53-2

Upstream product

• 62-53-3 aniline 
• 39629-86-2 5-oxo-1-phenyl-3-pyrrolidinecarboxylic acid 
• 97-65-4 2-methylenesuccinic acid 
• 93-90-3 N-(2-hydroxyethyl)-N-methylaminobenzene 
• 122-98-5 2-Anilinoethanol 
• 64320-92-9 methyl 5-oxo-1-phenylpyrrolidine-3-carboxylate 
• 103-01-5 N-Phenylglycine 
• 115011-74-0 N-phenyloxazolidin-5-one 
• 292638-85-8 acrylic acid methyl ester 

Downstream Products

• 933709-26-3 1-phenylpyrrolidine-3-carboxylic acid 

Relevant academic research and scientific papers

1-CYANO-PYRROLIDINE DERIVATIVES AS DUB INHIBITORS

The present invention relates to novel compounds and methods for the manufacture of inhibitors of deubiquitylating enzymes (DUBs). In particular, the invention relates to the inhibition of ubiquitin C-terminal hydrolase 30 or ubiquitin specific peptidase 30 (USP30). The novel compounds have formula (I): (Formula (I)) or are pharmaceutically acceptable salts thereof, wherein: R1a, R1b, R1c, R1d, R1e and R1f each independently represent hydrogen, optionally substituted C1-C6 alkyl or optionally substituted C3-C4 cycloalkyl, or R1b and R1c together form an optionally substituted C3-C6 cycloalkyl ring, or R1d and R1e together form an optionally substituted C3-C6 cycloalkyl ring; R2 represents hydrogen or optionally substituted C1-C6 alkyl; A represents an optionally further substituted 5 to 10 membered monocyclic or bicyclic heteroaryl, heterocyclyl or aryl ring; L represents a covalent bond or linker; B represents an optionally substituted 3 to 10 membered monocyclic or bicyclic heterocyclyl, heteroaryl, cycloalkyl or aryl ring; and when -A-L-B is at position x attachment to A is via a carbon ring atom of A, and either: A cannot be triazolopyridazinyl, triazolopyridinyl, imidazotriazinyl, imidazopyrazinyl or pyrrolopyrimidinyl; or B cannot be substituted with phenoxyl; or B cannot be cyclopentyl when L is an oxygen atom.

Transition Metal-Catalysed Intramolecular Carbenoid C?H Insertion for Pyrrolidine Formation by Decomposition of α-Diazoesters

The use of Pd-, Rh(II)- and Ru(II)-based catalysts has been explored in the transition metal-catalysed intramolecular carbenoid C?H insertion of α-diazoesters leading to pyrrolidines. Although the outcome of the reaction was highly substrate-dependent, in general, it was possible to control the chemoselectivity of the process towards pyrrolidines by adequate catalyst selection. The Pd(0)-catalysts were as efficient as [Rh(Ph3CCO2)2]2 in promoting the C(sp3)?H insertion of ortho-substituted anilines. In contrast, for anilines bearing meta- and para-substituents, the Rh(II)-catalyst provided the best chemoselectivities and reaction yields. On the other hand, [Ru(p-cymene)Cl2]2 was the most efficient catalyst for the insertion reaction of the N-benzyl-N-phenyl and N,N-dibenzyl α-diazoesters, while the C(sp3)?H insertion of the N-benzylsulfonamide substrate was only promoted by [Rh(Ph3CCO2)2]2. According to density functional theory (DFT) calculations, the mechanism involved in the Pd(0)- and Ru(II)-catalysed C(sp3)?H insertions differs considerably from that typically proposed for the Rh(II)-catalysed transformation. Whereas the Pd(0)-catalysed reaction involves a Pd-mediated 1,5-H migration from the C(sp3)?H bond to the carbenoid carbon atom leading to the formal oxidation of the transition metal, a Ru(II)-promoted Mannich type reaction involving a zwitterionic intermediate seems to be operative in the Ru(II)-catalysed transformation. (Figure presented.).

Palladium-catalyzed intramolecular carbene insertion into C(sp3)-H bonds

A palladium-catalyzed carbene insertion into C(sp3)-H bonds leading to pyrrolidines was developed. The coupling reaction can be catalyzed by both Pd0 and PdII, is regioselective, and shows a broad functional group tolerance. This reaction is the first example of palladium-catalyzed C(sp3)-C(sp3) bond assembly starting from diazocarbonyl compounds. DFT calculations revealed that this direct C(sp3)-H bond functionalization reaction involves an unprecedented concerted metalation-deprotonation step. Pd in action: Palladium has been used to catalyze the C(sp3)-H insertion of metal carbenoids derived from α-diazoesters to form pyrrolidines through intramolecular assembly of C(sp3)-C(sp3) bonds. A reaction mechanism involving a metalation-deprotonation step instead of the usual concerted but asynchronous process is proposed.

INDOLE AMIDE DERIVATIVES AND RELATED COMPOUNDS FOR USE IN THE TREATMENT OF NEURODEGENERATIVE DISEASES

This invention provides novel compounds and the novel compounds for use as a medicine, more in particular for the prevention or treatment of neurodegenerative disorders, more specifically certain neurological disorders, such as disorders collectively known as tauopathies, and disorders characterised by cytotoxic α-synuclein amyloidogenesis. The present invention also relates to the use of said novel compounds for the manufacture of medicaments useful for treating such neurodegenerative disorders. The present invention further relates to pharmaceutical compositions including said novel compounds and to methods for the preparation of said novel compounds.

Parent and N-substitued azomethine ylides from α-amino acids and formaldehyde. An easy access to 2,5-unsubstituted pyrrolidines. Evidence for oxazolidin-5-ones as direct precursor of these reactive intermediates

Formaldehyde reacts with α-amino acids and electron deficient alkenes to produce pyrrolidines.Azomethine ylides involved as intermediates in these reactions have been generated from isolated oxazolidin-5-ones which can be considered as the direct precursors of these ylides.