142589-43-3

Upstream product

• 32150-91-7 phthaloyl-L-phenylalanyl chloride 
• 6033-32-5 (S)-2-amino-6-hydroxyhexanoic acid 
• 5458-06-0 5-(4-hydroxybutyl)hydantoin 
• 110-87-2 3,4-dihydro-2H-pyran 
• 167090-40-6 (S)-2-amino-6-hydroxy-hexanoic acid methyl ester 
• 5123-55-7 Nα-phthaloyl-L-phenylalanine 
• 869588-52-3 (S)-N-[2-(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)]-1-oxo-3-(phenylpropyl)-allyl-(S)-glycine methyl ester 
• 201230-82-2 carbon monoxide 
• 142589-42-2 (S)-N-[2-(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)-1-oxo-3-phenylpropyl]-6-hydroxy-(S)-norleucine methyl ester 

Downstream Products

• 111581-88-5 [S(R*,R*)]-1-[2-(1,3-Dihydro-1,3-dioxo-2H-isoindol-2-yl)-1-oxo-3-phenylpropyl]-1,2,3,4-tetrahydro-2-pyridinecarboxylicacid, methyl ester 

Relevant academic research and scientific papers

HYDROFORMYLATION PROCESS FOR PHARMACEUTICAL INTERMEDIATE

The invention relates to an improved process for the preparation of an advanced synthetic intermediate of ACE inhibitors. In one aspect, the present invention is based on a novel process for the preparation of an aldehyde of formula (I), wherein (N)PrG is a protected amino group, R is an alkyl or aralkyl group and X1-4 are each independently H or a non-reacting substituent, which comprises hydroformylation of an α-olefin of formula (II), by reaction with syngas (CO/H2) in the presence of, as catalyst, a group VIII transition metal complex of a phosphorus-containing ligand. Aldehyde (I), the product of linear hydroformylation, is formed in preference to aldehyde (III). In another aspect of the invention, α-olefin (II) is a novel composition. The process to convert (II) to (I) enables an efficient manufacturing route to MDL 28,726 and analogues.

N-formyl hydroxylamine containing compounds useful as ACE inhibitors and/or NEP inhibitors

N-formyl hydroxylamines are provided which have the structure wherein R is H, alkyl, alkenyl, aryl-(CH2)p—, heteroaryl-(CH2)p— or cycloheteroalkyl-(CH2)p— R1is H or COR2where R2is alkyl, aryl-(CH2)p—, cycloheteroalkyl-(CH2)p—, heteroaryl-(CH2)p—, alkoxy or cycloalkyl-(CH2)p—, p is 0 to 8, and A is a dipeptide derived from an amino acid or is a conformationally restricted dipeptide mimic. The above compounds are useful in treating hypertension congestive heart failure, renal failure, and hepatic cirrhosis.

Process development in the synthesis of the ACE intermediate MDL 28,726

MDL 28,726 is a key intermediate in the synthesis of the ACE inhibitors MDL 27,210A and MDL 100,240. An efficient nine-step synthesis of this tricyclic acid, which has three chiral centers, was developed beginning with 3,4-dihydro-2H-pyran. A key step in the synthesis features an enzyme-catalyzed resolution of the lithium salt of the W-trifluoroacetamide of (A,5)-6-hydroxynorleucine. All of the steps were optimized and completed in reactor equipment using environmentally acceptable processes. Process development of this route is described.