203917-99-1

Basic information

• Product Name: rac-S-1255
• Synonyms: rac-S-1255
• CAS NO: 203917-99-1
• Molecular Weight: 460.483
• Mol File: 203917-99-1.mol
• Article Data: 3

Chemical Properties

• CAS DataBase Reference: rac-S-1255(CAS DataBase Reference)
• NIST Chemistry Reference: rac-S-1255(203917-99-1)
• EPA Substance Registry System: rac-S-1255(203917-99-1)

Safety Data

• Hazardous Substances Data: 203917-99-1(Hazardous Substances Data)

Upstream product

• 203919-37-3 methyl 2-(benzo[1,3]dioxol-5-yl)-6-isopropoxy-4-(trifluoromethanesulfonyloxy)-2H-chromene-3-carboxylate 
• 203919-40-8 2-(benzo[1,3]dioxol-5-yl)-6-isopropoxy-4-methoxy-2H-chromene-3-carbaldehyde 
• 203919-39-5 2-(benzo[1,3]dioxol-5-yl)-4-chloro-6-isopropoxy-2H-chromene-3-carbaldehyde 
• 203919-38-4 2-(benzo[1,3]dioxol-5-yl)-6-isopropoxychroman-4-one 
• 152810-05-4 5-isopropoxy-2-hydroxyacetophenone 
• 120-57-0 piperonal 
• 104-92-7 1-bromo-4-methoxy-benzene 
• 203917-88-8 2-(benzo[1,3]dioxol-5-yl)-6-isopropoxy-4-methoxy-2H-chromene-3-carboxylic acid 
• 203917-98-0 methyl 2-(benzo[1,3]dioxol-5-yl)-6-isopropoxy-4-(4-methoxy-phenyl)-2H-chromen-3-carboxylate 

Relevant articles and documents

Practical enantioselective synthesis of endothelin antagonist S-1255 by dynamic resolution of 4-methoxychromene-3-carboxylic acid intermediate

A practical multikilogram-scale synthesis of enantiomerically pure S-1255 (1), a potent and orally active ETA receptor antagonist, is described. Utilizing readily available starting materials and reagents, the entire sequence of reactions starting from 2,5-dihydroxyacetophenone 8 proceeded under mild conditions to give 1 in an excellent chemical yield (8 steps, 41% overall yield) and in a high enantiopurity (98% ee). The crucial step of the synthesis is a dynamic resolution of key intermediate 16. (R)-Methoxy acid (R)-16 having 97-99% ee was obtained in 83-84% yield from racemic 16 as a crystalline (1S,2R)-(+)-norephedrine or (+)-cinchonine salt by the dynamic resolution comprising concurrent crystallization and in situ racemization. A mechanism of the dynamic resolution through a ring-opened zwitterionic intermediate is discussed. In the final synthetic step, an effective carbon - carbon bond formation between the C4 carbon and the p-anisyl group was accomplished by a conjugate addition - elimination reaction of Grignard reagent 3 to (R)-16 to give 1 having 98% ee. Owing to high efficiencies of functional group transformations, carbon - carbon bond formations, and the dynamic resolution, the synthesis required no chromatographic purification and was amenable to a multikilogram-scale preparation. Several kilograms of 1 for clinical trials were successfully prepared by this process.

Chromene-3-carboxylate derivatives

The present invention provides a compound of the formula (I): wherein R1, R2, R3and R4are each independently hydrogen, optionally substituted alkyl, hydroxy, optionally substituted alkoxy or the like, R5/s