CP-B, CMP-3
(2S)-2-[(3R)-3-羟基-4-[3-(三氟甲基)苯基]丁基]-5-氧代-1-吡咯烷庚酸Chemical Name: 7-[2(S)-[3(R)-Hydroxy-4-[3-(trifluoromethyl)phenyl]butyl]-5-oxopyrrolidin-1-yl]heptanoic acid
CAS No. 346672-61-5
项目整合开发状态: Preclinical
项目研究机构: Pfizer (Originator)
合成路线:Alkylation of (R)-5-(t-butyldimethylsilyloxymethyl)pyrrolidin-2-one (I) with ethyl 7-bromoheptanoate (II) affords the pyrrolidone-ester (III).After removal of the silyl protecting group of (III) with tetrabutylammonium fluoride,the resultant alcohol (IV) is oxidized to aldehyde (V) under modified Swern conditions,using DMSO/EDC
合成路线:[3-(Trifluoromethyl)phenyl]acetic acid (VI) is coupled to N,O-dimethylhydroxylamine to produce the N-methoxy amide (VII).Subsequent condensation of methoxyamide (VII) with dimethyl methylphosphonate (VIII) in the presence of BuLi leads to the oxo phosphonate (IX).Horner-Emmons condensation of phosphonate (IX) with aldehyde (V) furnishes enone (X).Diastereoselective reduction of (X) by means of catecholborane in the presence of (R)-2-methyl-CBS-oxazaborolidine in cold CH2Cl2 provides the allylic alcohol (XI) as the major isomer.Subsequent catalytic hydrogenation of (XI) gives the saturated alcohol (XII).Finally,basic hydrolysis of the ethyl ester group of (XII) produces the target carboxylic acid
📌 参考资料/链接：
参考文献标题:EP4 receptor selective agonists in the treatment of osteoporosis
文献作者:Thompson,D.D.; Lefker,B.A.; Cameron,K.O.; Ke,H.Z.(Pfizer Products Inc.)
参考来源:EP 1110949; JP 2001181210; WO 0146140
📄 详细内容
合成路线:Alkylation of (R)-5-(t-butyldimethylsilyloxymethyl)pyrrolidin-2-one (I) with ethyl 7-bromoheptanoate (II) affords the pyrrolidone-ester (III).After removal of the silyl protecting group of (III) with tetrabutylammonium fluoride,the resultant alcohol (IV) is oxidized to aldehyde (V) under modified Swern conditions,using DMSO/EDC
合成路线:[3-(Trifluoromethyl)phenyl]acetic acid (VI) is coupled to N,O-dimethylhydroxylamine to produce the N-methoxy amide (VII).Subsequent condensation of methoxyamide (VII) with dimethyl methylphosphonate (VIII) in the presence of BuLi leads to the oxo phosphonate (IX).Horner-Emmons condensation of phosphonate (IX) with aldehyde (V) furnishes enone (X).Diastereoselective reduction of (X) by means of catecholborane in the presence of (R)-2-methyl-CBS-oxazaborolidine in cold CH2Cl2 provides the allylic alcohol (XI) as the major isomer.Subsequent catalytic hydrogenation of (XI) gives the saturated alcohol (XII).Finally,basic hydrolysis of the ethyl ester group of (XII) produces the target carboxylic acid
参考文献标题:Discovery and bone anabolic activity of highly selective EP4 receptor prostaglandin E2 (PGE2) agonists
文献作者:Cameron,K.O.; Crawford,D.T.; DaSilva-Jardine,P.; et al.
参考来源:224th ACS Natl Meet (Aug 18 2002,Boston) 2002,Abst MEDI 307
产品链接: CAS No. 346672-61-5››