Iralukast sodium, CGP-45715A

7-[(2S,3E,5Z)-10-(4-乙酰基-3-羟基-2-丙基苯氧基)-1-羟基-1-[3-(三氟甲基)苯基]癸-3,5-二烯-2-基]硫基-4-氧代苯并吡喃-2-羧酸Chemical Name: 7-[(1R,2S)-10-(4-Acetyl-3-hydroxy-2-propylphenoxy)-1-hydroxy-1-(3-trifluoromethylphenyl)deca-3(E),5(Z)-dien-2-ylthio]-4-oxo-4H-1-benzopyran-2-carboxylic acid sodium salt
CAS No. 151581-24-7 (free acid)
项目整合开发状态: Phase II
项目研究机构: Novartis (Originator)
合成路线:The condensation of 3-(trifluoromethyl)benzaldehyde (I) with phosphonate (II) by means of NaH in THF gives the unsaturated ester (III),which is reduced with DIBAL in ethyl ether / hexane,yielding 3-[3-(trifluoromethyl)phenyl]allyl alcohol (IV).The Sharpless asymmetric epoxidation of (IV) affords the epoxyalcohol (V),which is oxidized with pyridine稴O3 to the corresponding aldehyde and condensed with phosphorane (A) to provide the unsaturated epoxyaldehyde (VI).The condensation of aldehyde (VI) with the pentylphosphonium derivative (VII) by means of NaNH2 in THF gives the corresponding adduct (VIII).The addition of 4-oxo-7-sulfanyl-4H-1-benzopyran-2-carboxylic acid methyl ester (IX) to the epoxide group of (VIII) by means of Et3N in methanol yields the expected alpha-hydroxy thioether (X),which is finally hydrolyzed with NaOH in THF/water to afford the target sodium salt.The intermediate pentylphosphonium derivative (VII) has been obtained by selective alkylation of 2,4-dihydroxy-3-propylacetophenone (XI) with 1,5-dibromopentane (XII) followed by reaction of the resulting ether with triphenylphosphine in refluxing toluene.