Edonentan hydrate, BMS-207940-02, BMS-207940(anhydrous)

艾多南坦单水合物 艾多南坦 Chemical Name: N-[2'-(4,5-Dimethylisoxazol-3-ylsulfamoyl)-4-(2-oxazolyl)biphenyl-2-ylmethyl]-N,3,3-trimethylbutyramide hydrate
CAS No. 264609-13-4, 210891-04-6 (anhydrous), 210891-08-0 (K salt), 210891-06-8 (Li salt), 210891-07-9 (Na salt)
项目整合开发状态: Phase II
项目研究机构: Bristol-Myers Squibb (Originator)
合成路线:The hydrolysis of N-(4,5-dimethyl-3-isoxazolyl)carbamic acid tert-butyl ester (I) with HCl in dioxane gives the corresponding amine (II),which is condensed with 2-bromophenylsulfonyl chloride (III) by means of DMAP in pyridine to yield the sulfonamide (IV).The alkylation of (I) with 2-methoxyethoxymethyl chloride (V) and NaH in DMF affords the N,N-disubstituted sulfonamide (VI),which is treated with trimethyl borate (VII) and BuLi in THF to provide the boronate (VIII).The condensation of (VIII) with 2-bromo-5-(2-oxazolyl)benzaldehyde (IX) by means of palladium tetrakis(triphenylphosphine) in hot toluene/ethanol gives the biphenyl derivative (X),which is deprotected by means of HCl in refluxing ethanol/water to yield the sulfonamide (XI).The reductive amination of (XI) with methylamine and NaBH(OAc)3 in dichloromethane/HOAc affords the secondary amine (XII),which is finally acylated with 3,3-dimethylbutyryl chloride and TEA in dichloromethane to furnish the target diamide.