393810-25-8

Basic information

• Product Name: L-Proline, 4-fluoro-5-oxo-, methyl ester, (4R)- (9CI)
• Synonyms: L-Proline, 4-fluoro-5-oxo-, methyl ester, (4R)- (9CI)
• CAS NO: 393810-25-8
• Molecular Formula: C₆H₈FNO₃
• Molecular Weight: 161.1310232
• Product Categories: GLYCINESCAFFOLD;PYRROLE;HALIDE
• Mol File: 393810-25-8.mol
• Article Data: 5

Chemical Properties

• Appearance: /
• CAS DataBase Reference: L-Proline, 4-fluoro-5-oxo-, methyl ester, (4R)- (9CI)(CAS DataBase Reference)
• NIST Chemistry Reference: L-Proline, 4-fluoro-5-oxo-, methyl ester, (4R)- (9CI)(393810-25-8)
• EPA Substance Registry System: L-Proline, 4-fluoro-5-oxo-, methyl ester, (4R)- (9CI)(393810-25-8)

Safety Data

• Hazardous Substances Data: 393810-25-8(Hazardous Substances Data)

Upstream product

• 203866-18-6 methyl (2S,4R)-N-(tert-butyloxy)carbonyl-4-fluoropyrrolidine-2-carboxylate 
• 74844-91-0 (2S,4S)-N-tert-butoxycarbonyl-4-hydroxyproline methyl ester 
• 393810-24-7 (3R,5S)-3-fluoro-5-hydroxymethyl-2-pyrrolidinone 
• 17342-08-4 (S)-Pyroglutaminol 
• 105526-85-0 (S)-5-(trityloxymethyl)pyrrolidin-2-one 
• 186581-53-3 diazomethane 
• 237076-75-4 (2S,4R)-4-fluoro-5-oxo-pyrrolidine-2-carboxylic acid 

Downstream Products

• 237076-75-4 (2S,4R)-4-fluoro-5-oxo-pyrrolidine-2-carboxylic acid 
• 32563-24-9 (2S,4R)-L-erythro-4-fluoroglutamic acid 

Relevant articles and documents

Tricyclic-Carbocyclic RORγt Inverse Agonists - Discovery of BMS-986313

SAR efforts directed at identifying RORγt inverse agonists structurally different from our clinical compound 1 (BMS-986251) led to tricyclic-carbocyclic analogues represented by 3-7 and culminated in the identification of 3d (BMS-986313), with structural differences distinct from 1. The X-ray co-crystal structure of 3d with the ligand binding domain of RORγt revealed several key interactions, which are different from 1. The in vitro and in vivo PK profiles of 3d are described. In addition, we demonstrate robust efficacy of 3d in two preclinical models of psoriasis - the IMQ-induced skin lesion model and the IL-23-induced acanthosis model. The efficacy seen with 3d in these models is comparable to the results observed with 1.

TRICYCLIC SULFONES AS ROR GAMMA MODULATORS

There are described RORγ modulators of the formula (I), or stereoisomers, tautomers, pharmaceutically acceptable salts, solvates, or prodrugs thereof, wherein all substituents are defined herein. Also provided are pharmaceutical compositions comprising the same. Such compounds and compositions are useful in methods for modulating RORγ activity in a cell and methods for treating a subject suffering from a disease or disorder in which the subject would therapeutically benefit from modulation of RORγ activity, for example, autoimmune and/or inflammatory disorders.

Electrophilic fluorination of pyroglutamic acid derivatives: Application of substrate-dependent reactivity and diastereoselectivity to the synthesis of optically active 4-fluoroglutamic acids

Electrophilic fluorination of enantiomerically pure 2-pyrrolidinones (4) derived from (L)-glutamic acid has been investigated as a method for the synthesis of single stereoisomers of 4-fluorinated glutamic acids. Reaction of the lactam enolate derived from 9 with NFSi results in a completely diastereoselective monofluorination reaction to yield the monocyclic trans-substituted α-fluoro lactam product 21. Unfortunately, a decreased kinetic acidity in 21 and other structurally related monofluorinated products renders them resistant to a second fluorination. In contrast, the bicyclic lactam 12 is readily difluorinated under the standard conditions described to yield the α,α-difluoro lactam 24. The difference in reactivity between the two types of related lactams is attributed mainly to the presence or lack of a steric interaction between the base used for deprotonation and the protecting group present in the pyrrolidinone substrates. This conclusion was reached based on analysis of the X-ray crystal structure of 21, molecular modeling, and experimental evidence. The key intermediates 21 and 24 are converted to (2S,4R)-4-fluoroglutamic acid and (2S)-4,4-difluoroglutamic acid, respectively.