1197357-98-4

Upstream product

• 1197357-97-3 methyl 4-(difluoromethoxy)-3-(pyridin-2-ylethynyl)benzoate 
• 1131614-23-7 4-difluoromethoxy-3-iodo-benzoic acid methyl ester 
• 15126-06-4 methyl 3-iodo-4-hydroxybenzoate 

Downstream Products

• 1197358-17-0 1-{[4-(difluoromethoxy)-3-(pyridin-2-ylethynyl)phenyl]carbonyl}-4-pyridin-2-ylpiperazine 
• 1253291-28-9 (4-(difluoromethoxy)-3-(pyridin-2-ylethynyl)phenyl)(5H-pyrrolo[3,4-b]pyridin-6(7H)-yl)methanone hydrochloride salt 
• 1253291-12-1 (4-difluoromethoxy-3-pyridin-2-ylethynyl-phenyl)-(5,7-dihydro-pyrrolo[3,4-b]pyridin-6-yl)-methanone 

Relevant academic research and scientific papers

Difluoromethylation of Phenols and Thiophenols with the S-(Difluo-romethyl)sulfonium Salt: Reaction, Scope, and Mechanistic Study

A facile and practical approach for the difluoromethylation of phenols and thiophenols was described. Making use of the recently developed bench-stable S-(difluoromethyl)sulfonium salt as the difluorocarbene precursor, a wide variety of diversely functionalized phenols and thiophenols were readily converted to their corresponding aryl difluoromethyl ethers in good to excellent yields in the presence of lithium hydroxide. Chemoselectivity of various O,S-nucleophiles toward difluorocarbene was systematically studied, suggesting the reactivity order ArS- > RS-, ArO- > ROH > RO-, ArSH, ArOH, RSH.

A robust process for an mGluR5 negative allosteric modulator: Difluoromethylation and sonogashira coupling on large scale

The development of the potent and selective mGluR5 negative allosteric modulator (NAM) 1 is described. Key features in the process, which has been implemented on a multikilogram scale, include a high-temperature difluoromethylation reaction, a Sonogashira coupling, and careful control of residual Pd and Cu in the final API. Due to the relative nonpolar nature of the intermediates, water-miscible solvents were employed in all four steps to allow for direct crystallizations upon reaction completion. In addition, several crystalline morphologies of the API were discovered, and the isolation of the desired form II will be discussed.

BISARYL ALKYNYLAMIDES AS NEGATIVE ALLOSTERIC MODULATORS OF METABOTROPIC GLUTAMATE RECEPTOR 5 (MGLUR5)

Disclosed are compounds of Formula (I): pharmaceutical compositions containing compounds of Formula I, and the use of compounds of Formula (I) to treat diseases and disorders including schizophrenia, paranoia, depression, manic-depressive illness and anxiety wherein W1-W5, X1-X4, Y, Z1-Z5, m, n, p, and R1-R6 in Formula (I) are defined in the specification.

PIPERAZINE METABOTROPIC GLUTAMATE RECEPTOR 5 (MGLUR5) NEGATIVE ALLOSTERIC MODULATORS FOR ANXIETY/DEPRESSION

The present teachings relate to piperazine metabotropic glutamate receptor 5 (mGluR5) negative allosteric modulators having Formula (I); wherein the constituent variables are as defined herein. The present teachings further relate to methods for the preparation of the compounds, and to methods for using the compounds for treatment of diseases and disorders including schizophrenia, paranoia, depression, manic-depressive illness and anxiety.