新产品编号:638055
Chemical Name: 3-[2(R)-(Benzofuran-2-ylmethoxycarboxamido)-2-methyl-3-oxo-3-[1(S)-phenylethylamino]propyl]-1H-indole-1-carboxylic acid 4-(phosphonooxymethyl)benzoyloxymethyl ester disodium salt
CAS No. 247017-93-2, 247017-92-1 (free acid)
项目整合开发状态: Preclinical
项目研究机构: Pfizer (Originator)
合成路线:Preparation of the intermediate silver carboxylate salt (V) is by esterification of p-(chloromethyl)benzoic acid (I) employing diazomethane,followed by displacement of the chloro group by NaI-furnished iodo ester (III).Reaction of iodide (III) with silver dibenzyl phosphate produced phosphate ester (IV).The methyl ester group of (IV) was then hydrolyzed with LiOH and subsequently converted to the silver carboxylate salt by means of AgNO3.
合成路线:Conversion of the known compound (VI) into the title prodrug is by the following procedure: Treatment of the potassium salt of (VI) with (chloromethyl) chloroformate (A) at -78 C gave the chloromethoxycarbonyl derivative (VII),which was further converted to the iodo analogue (VIII) under Finkelstein conditions.Compound (VIII) was then coupled with the silver carboxylate (V) in refluxing toluene to provide ester (IX).The benzyl ester groups of (IX) were deprotected by transfer hydrogenolysis,and the phosphoric acid derivative was finally treated with NaOH to yield the title sodium phosphate salt.
📌 参考资料/链接：
参考文献标题:Prodrugs of benzofuranylmethyl carbamate NK1 antagonists
文献作者:Chan,O.H.; Chen,M.H.G.; Goel,O.P.; Hershenson,F.M.; Zhu,Z.(Pfizer Inc.)
参考来源:WO 9952903
📄 详细内容
合成路线:Preparation of the intermediate silver carboxylate salt (V) is by esterification of p-(chloromethyl)benzoic acid (I) employing diazomethane,followed by displacement of the chloro group by NaI-furnished iodo ester (III).Reaction of iodide (III) with silver dibenzyl phosphate produced phosphate ester (IV).The methyl ester group of (IV) was then hydrolyzed with LiOH and subsequently converted to the silver carboxylate salt by means of AgNO3.
合成路线:Conversion of the known compound (VI) into the title prodrug is by the following procedure: Treatment of the potassium salt of (VI) with (chloromethyl) chloroformate (A) at -78 C gave the chloromethoxycarbonyl derivative (VII),which was further converted to the iodo analogue (VIII) under Finkelstein conditions.Compound (VIII) was then coupled with the silver carboxylate (V) in refluxing toluene to provide ester (IX).The benzyl ester groups of (IX) were deprotected by transfer hydrogenolysis,and the phosphoric acid derivative was finally treated with NaOH to yield the title sodium phosphate salt.
参考文献标题:Phosphate prodrugs of PD154075
文献作者:Zhu,Z.; Chen,H.G.; Goe,O.P.; Chan,O.H.; Stilgenbauer,L.A.; Stewart,B.H.
参考来源:Bioorg Med Chem Lett 2000,10(10),1121