481055-29-2

Upstream product

• 481055-28-1 (2S)-2-amino-3,3-bis(4-fluorophenyl) propanoic acid 
• 24424-99-5 di-tert-butyl dicarbonate 
• 918625-32-8 4-fluoro-β-(4-fluorophenyl)-L-phenylalanine hydrochloride 
• 345-92-6 4,4'-Difluorobenzophenone 
• 1416247-69-2 C₁₉H₁₉F₂NO₃ 

Downstream Products

• 811432-66-3 denagliptin tosylate 
• 483368-24-7 tert-butyl {(1S)-1-[bis(4-fluorophenyl)methyl]-2-[(2S)-cyano-(4S)-fluoro-1-pyrrolidinyl]-2-oxoethyl}carbamate 

Relevant academic research and scientific papers

The large-scale synthesis of (S)-N-boc-bis(4-fluorophenyl)alanine

The synthesis of (S)-N-Boc-bis(4-fluorophenyl)alanine, an intermediate in the synthesis of denagliptin, is described from the synthesis of a 12 g proof of principle sample to a >900 kg cGMP manufacturing campaign. The chiral centre was established by the asymmetric hydrogenation of the sterically crowded precursor, ethyl 2-acetamido-3,3-bis(4-fluorophenyl)acrylate. The ability to isolate the various intermediates in a physical form that would readily allow filtration, washing, and ultimately purification underpinned the successful manufacturing campaign.

Production method of optically active dephenylalanine compounds

Optically active diphenylalanine compounds may be conveniently prepared in a good yield by reacting a diphenylalanine compound represented by formula (1) with an optically active amine compound represented by formula (2) in the presence of an organic solvent to give a diastereomeric salt represented by formula (5) and then treating the diastereomeric salt under acidic conditions to give an optically active diphenylalanine compound represented by formula (3): wherein each symbol is as defined in the specification.

Production method of optically active diphenylalanine compounds

The present invention provides a production method including reacting a diphenylmethylene halide compound represented by the following formula (1) with a malonic acid diester compound represented by the following formula (2) in an organic solvent selected

(2S,4S)-4-FLUORO-1-[4-FLUORO-BETA-(4-FLUOROPHENYL)-L-PHENYLALANYL]-2-PYRROLIDINECARBONITRILE P-TOLUENESULFONIC ACID SALT AND ANHYDROUS CRYSTALLINE FORMS THEREOF

The present invention includes anhydrous crystalline forms of (2S,4S)-4-fluoro-1-[4-fluoro-β-(4-fluorophenyl)-L-phenylalanyl]-2-pyrrolidinecarbonitrile p-toluenesulfonic acid salt.