1204331-63-4

Upstream product

• 110-86-1 pyridine 
• 1422252-48-9 1-(4-(2-(trifluoromethyl)phenyl)piperidin-1-yl)ethanone 
• 1422252-47-8 1-(4-(2-(trifluoromethyl)phenyl)pyridin-1(4H)-yl)ethanone 
• 67-56-1 methanol 
• 201230-82-2 carbon monoxide 
• 1422252-49-0 1-(4-(4-bromo-2-(trifluoromethyl)phenyl)piperidin-1-yl)ethanone 
• 375853-82-0 tert-Butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-1(2H)-pyridinecarboxylate 
• 138647-49-1 4-Trifluoromethanesulfonyloxy-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester 
• 79099-07-3 N-tert-butyloxycarbonylpiperidin-4-one 
• 1204331-48-5 4-(4-methoxycarbonyl-2-trifluoromethylphenyl)piperidine-1-carboxylic acid tert-butyl ester 
• 1204331-26-9 4-(4-methoxycarbonyl-2-trifluoromethylphenyl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester 
• 161622-14-6 4-bromo-3-(trifluoromethyl)benzoic acid 
• 107317-58-8 4-bromo-3-trifluoromethylbenzoic acid methyl ester 
• 1204331-36-1 4-piperidin-4-yl-3-trifluoromethyl-benzoic acid methyl ester 

Downstream Products

• 1204329-34-9 N-[4-(1-acetyl-piperidin-4-yl)-3-trifluoromethylbenzoyl]guanidine 
• 1422252-53-6 C₁₅H₁₆F₃NO₃ 
• 1422252-54-7 C₃₁H₃₃F₆N₅O₄ 
• 1204329-34-9 4-(1-acetylpiperidin-4-yl)-N-(diaminomethylene)-3-(trifluoromethyl)benzamide 
• 1422252-46-7 C₁₆H₁₉F₃N₄O₂*ClH 

Relevant academic research and scientific papers

Synthesis of a sodium-hydrogen exchange type 1 inhibitor: An efficient Cu-catalyzed conjugated addition of a Grignard reagent to an acetyl pyridinium salt

A facile and economical five-step process for the synthesis of a sodium-hydrogen exchange type I inhibitor (NHE-1) was developed from readily available starting materials in 43% overall yield. Key transformations included a highly efficient copper-catalyzed conjugate addition of 2- trifluoromethylphenyl Grignard reagents to acetyl pyridinium salts, a facile hydrogenation of 4-aryl dihydropyridines, a regioselective aromatic bromination, an efficient palladium-catalyzed carbonylation of aryl bromides, and a high-yielding acyl guanidine formation. A safe and scalable protocol for preparation of 2-trifluoromethyl phenyl Grignard reagent was developed, and a facile method for controlling the palladium content with N-acetyl-L-cysteine as the scavenger was demonstrated. Process issues in controlling the formation of a key diacylation side product during acyl guanidine formation are also addressed.

PYRROLIDINYL AND PIPERIDINYL COMPOUNDS USEFUL AS NHE-1 INHIBITORS

Disclosed are compounds of formula (I) and compositions of the present invention which are inhibitors of the sodium proton exchanger isoform-1 (NHE-I). Also disclosed are methods of using and making the same.