CP-B, CMP-3, -Drug Synthesis Database

【结构式】

【药物名称】CP-B, CMP-3

【化学名称】7-[2(S)-[3(R)-Hydroxy-4-[3-(trifluoromethyl)phenyl]butyl]-5-oxopyrrolidin-1-yl]heptanoic acid

【CA登记号】346672-61-5

【分子式】C₂₂H₃₀F₃NO₄

【分子量】429.4839

【开发单位】Pfizer (Originator)

【药理作用】Bone Diseases, Treatment of, METABOLIC DRUGS, Treatment of Osteoporosis, Prostanoid EP4 Agonists

合成路线1 合成路线2

合成路线1

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

参考文献中间体

【1】 Cameron, K.O.; Crawford, D.T.; DaSilva-Jardine, P.; et al.; Discovery and bone anabolic activity of highly selective EP4 receptor prostaglandin E2 (PGE2) agonists. 224th ACS Natl Meet (Aug 18 2002, Boston) 2002, Abst MEDI 307.
【2】 Thompson, D.D.; Lefker, B.A.; Cameron, K.O.; Ke, H.Z. (Pfizer Products Inc.); EP4 receptor selective agonists in the treatment of osteoporosis. EP 1110949; JP 2001181210; WO 0146140 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	60581	(5R)-5-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-pyrrolidinone		C₁₁H₂₃NO₂Si	详情	详情
(II)	36428	ethyl 7-bromoheptanoate	29823-18-5	C₉H₁₇BrO₂	详情	详情
(III)	60582	ethyl 7-[(2R)-2-({[tert-butyl(dimethyl)silyl]oxy}methyl)-5-oxopyrrolidinyl]heptanoate		C₂₀H₃₉NO₄Si	详情	详情
(IV)	60583	ethyl 7-[(2R)-2-(hydroxymethyl)-5-oxopyrrolidinyl]heptanoate		C₁₄H₂₅NO₄	详情	详情
(V)	60584	ethyl 7-[(2R)-2-formyl-5-oxopyrrolidinyl]heptanoate		C₁₄H₂₃NO₄	详情	详情

合成路线2

[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

参考文献中间体

【1】 Cameron, K.O.; Crawford, D.T.; DaSilva-Jardine, P.; et al.; Discovery and bone anabolic activity of highly selective EP4 receptor prostaglandin E2 (PGE2) agonists. 224th ACS Natl Meet (Aug 18 2002, Boston) 2002, Abst MEDI 307.
【2】 Thompson, D.D.; Lefker, B.A.; Cameron, K.O.; Ke, H.Z. (Pfizer Products Inc.); EP4 receptor selective agonists in the treatment of osteoporosis. EP 1110949; JP 2001181210; WO 0146140 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(V)	60584	ethyl 7-[(2R)-2-formyl-5-oxopyrrolidinyl]heptanoate		C₁₄H₂₃NO₄	详情	详情
(VI)	60585	2-[3-(trifluoromethyl)phenyl]acetic acid		C₉H₇F₃O₂	详情	详情
(VII)	60586	N-methoxy-N-methyl-2-[3-(trifluoromethyl)phenyl]acetamide		C₁₁H₁₂F₃NO₂	详情	详情
(VIII)	13607	dimethyl methylphosphonate	756-79-6	C₃H₉O₃P	详情	详情
(IX)	60587	dimethyl 2-oxo-3-[3-(trifluoromethyl)phenyl]propylphosphonate		C₁₂H₁₄F₃O₄P	详情	详情
(X)	60588	ethyl 7-((5R)-2-oxo-5-{(E)-3-oxo-4-[3-(trifluoromethyl)phenyl]-1-butenyl}pyrrolidinyl)heptanoate		C₂₄H₃₀F₃NO₄	详情	详情
(XI)	60589	ethyl 7-((2R)-2-{(E,3S)-3-hydroxy-4-[3-(trifluoromethyl)phenyl]-1-butenyl}-5-oxopyrrolidinyl)heptanoate		C₂₄H₃₂F₃NO₄	详情	详情
(XII)	60590	ethyl 7-((2S)-2-{(3R)-3-hydroxy-4-[3-(trifluoromethyl)phenyl]butyl}-5-oxopyrrolidinyl)heptanoate		C₂₄H₃₄F₃NO₄	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)