149709-61-5

Upstream product

• 1012341-54-6 (2R/S,4S)-5-biphenyl-4-yl-4-tert-butoxycarbonylamino-2-methylpentanoic acid 
• 75-03-6 ethyl iodide 
• 1174131-30-6 (R)-5-biphenyl-4-yl-4-tert-butoxycarbonylamino-2-methylenepentandic acid ethyl ester 
• 153037-44-6 (S)-5-biphenyl-4-yl-4-tert-butoxycarbonylaminopentanoic acid ethyl ester 
• 74-88-4 methyl iodide 
• 1038924-77-4 (S)-2-biphenyl-4-ylmethyl-5-oxopyrrolidine-1-carboxylic acid tert-butyl ester 
• 929872-80-0 tert-butyl (R)-3-(4-hydroxyphenyl)-1-[methoxy(methyl)amino]-1-oxopropan-2-ylcarbamate 
• 70642-86-3 N-(tert-butoxycarbonyl)-D-tyrosine 
• 98-80-6 phenylboronic acid 

Downstream Products

• 1012341-50-2 (2R,4S)-5-[(1,1‘-biphenyl)-4-yl]-4-((tert-butoxycarbonyl)amino)-2-methylpentanoic acid 

Relevant academic research and scientific papers

BIPHENYL-SUBSTITUED 4-AMINO-BUTYRIC ACID DERIVATIVES AND THEIR USE IN THE SYNTHESIS OF NEP INHIBITORS

The invention relates to a novel process, novel process steps and novel intermediates useful in the synthesis of pharmaceutically active compounds, in particular neutral endopeptidase (NEP) inhibitors and prodrugs thereof.

Preparation method of anti-heart-failure drug intermediate

The invention discloses a preparation method of an anti-heart-failure drug intermediate (2R,4S)-5-([1,1'-biphenyl]-4-yl)-4-((tertbutyloxycarbonyl)amino)-2-methylpentanoic acid. Under catalysis of a transition metal catalyst bis(dicyclopentadiene)rhodium tetrafluoroborate and a ligand (CK004), butoxy carbonyl-D-tyrosine which is used as a raw material undergoes diastereoselective hydrogenation synthesis by the use of hydrogen to obtain chiral center; and a product obtained after recrystallization of the chiral center and hydroxide radical form a leaving group by the use of trifluoromethanesulfonic anhydride; and an intermediate V undergoes a coupling reaction by the use of phenylboronic acid so as to obtain the finished product. The invention provides a brand-new synthesis route of the anti-heart-failure drug intermediate. The reaction steps are easy to control, and stable industrial production preparation can be realized.

NEW PROCESSES

The invention relates to a new process for producing NEP inhibitors or prodrugs thereof, in particular NEP inhibitors comprising a γ-amino-δ-biphenyl-α-methylalkanoic acid, or acid ester, backbone. In detail, the new processes, according to the present invention, are ultimately related to the synthesis of intermediates to prepare the above NEP inhibitors, namely compounds according to formula (1), or salt thereof, wherein R1 and R2 are, independently of each other, hydrogen or a nitrogen protecting group, and R3 is a carboxyl group or an ester group, preferably carboxyl group or alkyl ester.