Gabapentin, DDS-2003, Goe-3450, CI-945, Neurontin, -Drug Synthesis Database

【结构式】

【药物名称】Gabapentin, DDS-2003, Goe-3450, CI-945, Neurontin

【化学名称】2-[1-(Aminomethyl)cyclohexyl]acetic acid

【CA登记号】60142-96-3

【分子式】C₉H₁₇NO₂

【分子量】171.24134

【开发单位】Pfizer (Originator), Labopharm (Formulation), National Institutes of Health (Codevelopment)

【药理作用】ANALGESIC AND ANESTHETIC DRUGS, Analgesic Drugs, Antiepileptic Drugs, Antimigraine Drugs, Fibromyalgia, Treatment of, Migraine, Prophylactic Treatment of, NEUROLOGIC DRUGS, Neurologic Drugs (Miscellaneous), Neuropathic Pain, Treatment of, Sensation Disorders, Treatment of

合成路线1 合成路线2

合成路线1

Reaction of cyclohexenone (I) with ethyl cyanoacetate (A) in the presence of ammonia affords the Guareschi salt (II), which is hydrolyzed and decarboxylated to give 1,1-cyclohexanediacetic acid (III). The anhydride (IV) can be treated either with methanol to yield the halfester (V), or with hydroxylamine to afford the N-hydroxyimide (VII). The halfester (V) is subjected to a Curtius type rearrangement to give the isocyanate (VI), which is hydrolyzed to the amino acid hydrochloride (Xl).

参考文献中间体

【1】 Satzinger, G.; Hartenstein, J. (Pfizer Inc.); Cyclic sulphonyloxyimides. DE 2611690; ES 457050; FR 2344540; GB 1575709; JP 52113977; US 4152326 .
【2】 Satzinger, G.; Hartenstein, J.; Herrmann, M.; Heldt, W. (Pfizer Inc.); Cyclic aminoacids. DE 2460891; ES 443723; FR 2294697; GB 1465229; JP 51088940; US 4024175 .
【3】 Castaner, J.; Serradell, M.N.; Gabapentin. Drugs Fut 1984, 9, 6, 418.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	11877	Cyanoacetic acid ethyl ester; Ethyl 2-cyanoacetate; Ethyl cyanoacetate; Ethyl isocyanacetate	105-56-6	C₅H₇NO₂	详情	详情
(I)	11059	Cyclohexanone	108-94-1	C₆H₁₀O	详情	详情
(II)	30541	3',5'-Dicyano-2',4'-dioxospiro[cyclohexane-1,4'-piperidide] ammonium salt		C₁₂H₁₆N₄O₂	详情	详情
(III)	30542	2-[1-(2-hydroxy-2-oxoethyl)cyclohexyl]acetic acid	4355-11-7	C₁₀H₁₆O₄	详情	详情
(IV)	30543	3-oxaspiro[5.5]undecane-2,4-dione		C₁₀H₁₄O₃	详情	详情
(V)	30544	2-[1-(2-methoxy-2-oxoethyl)cyclohexyl]acetic acid		C₁₁H₁₈O₄	详情	详情
(VI)	30545	methyl 2-[1-(isocyanatomethyl)cyclohexyl]acetate		C₁₁H₁₇NO₃	详情	详情
(XI)	30546	2-[1-(aminomethyl)cyclohexyl]acetic acid	60142-96-3	C₉H₁₇NO₂	详情	详情

合成路线2

The same product can be obtained from reaction of cyclohexenone (I) with ethyl cyanoacetate (A) in the presence of ammonia affords the Guareschi salt (II), which is hydrolyzed and decarboxylated to give 1,1-cyclohexanediacetic acid (III). The anhydride (IV) can be treated with the N-hydroxyimide (VII) via a Lossen type rearrangement by conversion of (VII) to N-benzenesulfonyloxylmide (VIII) and subsequent reaction with triethylamine in methanol followed by hydrolysis of the urethanester (IX). The free amino acid is finally obtained from the hydrochloride (X) via anion exchange.

参考文献中间体

【1】 Satzinger, G.; Hartenstein, J. (Pfizer Inc.); Cyclic sulphonyloxyimides. DE 2611690; ES 457050; FR 2344540; GB 1575709; JP 52113977; US 4152326 .
【2】 Satzinger, G.; Hartenstein, J.; Herrmann, M.; Heldt, W. (Pfizer Inc.); Cyclic aminoacids. DE 2460891; ES 443723; FR 2294697; GB 1465229; JP 51088940; US 4024175 .
【3】 Castaner, J.; Serradell, M.N.; Gabapentin. Drugs Fut 1984, 9, 6, 418.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	11877	Cyanoacetic acid ethyl ester; Ethyl 2-cyanoacetate; Ethyl cyanoacetate; Ethyl isocyanacetate	105-56-6	C₅H₇NO₂	详情	详情
(I)	11059	Cyclohexanone	108-94-1	C₆H₁₀O	详情	详情
(II)	30541	3',5'-Dicyano-2',4'-dioxospiro[cyclohexane-1,4'-piperidide] ammonium salt		C₁₂H₁₆N₄O₂	详情	详情
(III)	30542	2-[1-(2-hydroxy-2-oxoethyl)cyclohexyl]acetic acid	4355-11-7	C₁₀H₁₆O₄	详情	详情
(IV)	30543	3-oxaspiro[5.5]undecane-2,4-dione		C₁₀H₁₄O₃	详情	详情
(VII)	30547	3-hydroxy-3-azaspiro[5.5]undecane-2,4-dione		C₁₀H₁₅NO₃	详情	详情
(VIII)	30548	3-[(phenylsulfonyl)oxy]-3-azaspiro[5.5]undecane-2,4-dione		C₁₆H₁₉NO₅S	详情	详情
(IX)	30549	methyl 2-(1-[[(methoxycarbonyl)amino]methyl]cyclohexyl)acetate		C₁₂H₂₁NO₄	详情	详情
(X)	30546	2-[1-(aminomethyl)cyclohexyl]acetic acid	60142-96-3	C₉H₁₇NO₂	详情	详情

Extended Information