CI-933, -Drug Synthesis Database

【结构式】

【药物名称】CI-933

【化学名称】1-(4-Methoxybenzoyl)-5-oxopyrrolidine-2-propionic acid
　　　　　　3-[1-(4-Methoxybenzoyl)-5-oxopyrrolidin-2-yl]propionic acid

【CA登记号】91829-95-7

【分子式】C₁₅H₁₇NO₅

【分子量】291.30644

【开发单位】Pfizer (Originator)

【药理作用】Cognition Disorders, Treatment of, NEUROLOGIC DRUGS

合成路线1 合成路线2

合成路线1

The esterification of bromoacetic acid (I) with benzyl alcohol (II) gives the corresponding ester (III), which by reaction with triphenylphosphine (IV) in hot toluene yields the phosphonium bromide (V). The reaction of (V) with NaOH in water-dichloromethane affords benzyl(triphenylphosphoranylidene) acetate (VI), which is submitted to a Wittig condensation with 5-(hydroxymethyl)-2-pyrrolidone (VII) in the presence of Dess-Martin periodinane (DMPI) giving benzyl 3-(5-oxo-2-pyrrolidinyl)-2(E) propenoate (VIII). The acylation of (VIII) with 4-methoxybenzoyl chloride (IX) by means of triethylamine in hot toluene yields the corresponding amide (X), which is finally hydrogenated and deprotected with H2 over Pd/C in THF.

参考文献中间体

【1】 Huang, C.C.; Synthesis of carbon-14 labeled 1-(4-methoxybenzoyl. J Label Compd Radiopharm 1987, 24, 6, 675.

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)	23660	2-Bromoacetic acid	79-08-3	C₂H₃BrO₂	详情	详情
(II)	18710	Benzyl alcohol; Phenylmethanol	100-51-6	C₇H₈O	详情	详情
(III)	12869	benzyl 2-bromoacetate	5437-45-6	C₉H₉BrO₂	详情	详情
(IV)	12437	Triphenylphosphine; Triphenyl phosphine	603-35-0	C₁₈H₁₅P	详情	详情
(V)	22667	[2-(benzyloxy)-2-oxoethyl](triphenyl)phosphonium bromide		C₂₇H₂₄BrO₂P	详情	详情
(VI)	22668	benzyl 2-(triphenylphosphoranylidene)acetate		C₂₇H₂₃O₂P	详情	详情
(VII)	10079	5-(Hydroxymethyl)-2-pyrrolidinone	62400-75-3	C₅H₉NO₂	详情	详情
(VIII)	22670	benzyl (E)-3-(5-oxo-2-pyrrolidinyl)-2-propenoate		C₁₄H₁₅NO₃	详情	详情
(IX)	22671	4-Methoxybenzoyl chloride; p-Methoxybenzoyl chloride; 4-Anisoyl chloride	100-07-2	C₈H₇ClO₂	详情	详情
(X)	22672	benzyl (E)-3-[1-(4-methoxybenzoyl)-5-oxo-2-pyrrolidinyl]-2-propenoate		C₂₂H₂₁NO₅	详情	详情

合成路线2

The partial hydrolysis of perhydropyrrolizine-3,5-dione (I) in the presence of benzyl alcohol (II) by means of aqueous concentrated HCl at 98 C gives benzyl 5-oxopyrrolidine-2-propenoate (III), which is condensed with 4-methoxybenzoyl chloride (IV) by means of triethylamine in hot THF to afford benzyl 1-(4-methoxybenzoyl)-5-oxopyrrolidine-3-propanoate (V). Finally, this compound ls debenzylated by hydrogenolysis with H2 over Pd/C in THF.

参考文献中间体

【1】 (Pfizer Inc.); 1-Aroyl-5-oxo-2-pyrrolidinepropanoic acid derivs.. EP 0110575; ES 8600238 .
【2】 Castaner, J.; Serradell, M.N.; CI-933. Drugs Fut 1985, 10, 12, 972.

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)	29829	dihydro-1H-pyrrolizine-3,5(2H,6H)-dione		C₇H₉NO₂	详情	详情
(II)	18710	Benzyl alcohol; Phenylmethanol	100-51-6	C₇H₈O	详情	详情
(III)	29830	benzyl 3-(5-oxo-2-pyrrolidinyl)propanoate		C₁₄H₁₇NO₃	详情	详情
(IV)	22671	4-Methoxybenzoyl chloride; p-Methoxybenzoyl chloride; 4-Anisoyl chloride	100-07-2	C₈H₇ClO₂	详情	详情
(V)	29831	benzyl 3-[1-(4-methoxybenzoyl)-5-oxo-2-pyrrolidinyl]propanoate		C₂₂H₂₃NO₅	详情	详情

Extended Information