Rasagiline mesilate, TVP-1012, (+)-AGN-1135, -Drug Synthesis Database

【结构式】

【药物名称】Rasagiline mesilate, TVP-1012, (+)-AGN-1135

【化学名称】1(R)-(Propargylamino)indane methanesulfonate
　　　　　　1(R)-(2-Propynylamino)indane methanesulfonate
　　　　　　(R)-N-2-Propynyl-1-indanamine methanesulfonate

【CA登记号】161735-79-1, 136236-51-6 (free base)

【分子式】C₁₃H₁₇NO₃S

【分子量】267.34934

【开发单位】Teva (Originator), Lundbeck (Licensee), Eisai (Codevelopment)

【药理作用】Alzheimer's Dementia, Treatment of , Antiparkinsonian Drugs, Cognition Disorders, Treatment of, Extrapyramidal Disorders, Treatment of, NEUROLOGIC DRUGS, MAO-B Inhibitors

合成路线1 合成路线2 合成路线3

合成路线1

参考文献中间体

【1】 Reddy RP, Davies HM.2006. Dirhodium tetracarboxylates derived from adamantylglycine as chiral catalysts for enantioselective C-H aminations. Org Lert,8: 5013～5016

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)	55807	4-Nitrobenzenesulfonamide; p-Nitrobenzenesulfonamide	6325-93-5	C₆H₆N₂O₄S	详情	详情
(II)	66624	2,3-dihydro-1H-indene；1,2-hydrindene	496-11-7	C₉H₁₀	详情	详情
(III)	66625	(R)-N-(2,3-dihydro-1H-inden-1-yl)-4-nitrobenzenesulfonamide		C₁₅H₁₄N₂O₄S	详情	详情
(IV)	66626	(R)-N-(2,3-dihydro-1H-inden-1-yl)-4-nitro-N-(prop-2-yn-1-yl)benzenesulfonamide		C₁₈H₁₆N₂O₄S	详情	详情

合成路线2

参考文献中间体

【1】 Boulton LT, Lennon IC, Bahar E 2006. Process for the synthesis of enantiomeric (propynylamino) indan derivatives by asymmetric reduction of indanones to chiral indanols and subsequent amination with propargylamine. US 2006199974（本专利属于Teva PMrmaceutical Industries Ltd, Israel)

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)	23857	1-indanone	83-33-0	C₉H₈O	详情	详情
(II)	53590	1-Hydroxyhydrindene; 1-Hydroxyindan; 1-Indanol	6351-10-6	C₉H₁₀O	详情	详情

合成路线3

Rasagiline can be obtained by two related ways: 1) The alkylation of racemic 1-aminoindane with propagyl chloride (II) and K2CO3 in hot acetonitrile gives the racemic secondary amine (III), which is submitted to optical resolution by chromatography over Chiracel OJ and eluting with hexane/isopropanol (90:10). 2) By alkylation of (R)-1-aminoindane (IV) with propargyl chloride (or bromide) (II) as before.

参考文献中间体

【1】 Graul, A.; Castaner, J.; Rasagiline. Drugs Fut 1996, 21, 9, 903.
【2】 Youdim, M.B.H.; Finberg, J.P.M.; Levy, R.; Sterling, J.; Lerner, D.; Berger-Paskin, T. (Teva Pharmaceutical Industries Ltd.); R-Enantiomers of N-propargyl-1-aminoindan cpds., their preparation and pharmaceutical compsns. containing them. EP 0436492; JP 1991294248; US 5453446 .
【3】 Youdim, M.B.H.; Finberg, J.P.M.; Levy, R.; Sterling, J.; Lerner, D.; Berger-Paskin, T.; Yellin, H.; Veinberg, A. (Teva Pharmaceutical Industries Ltd.); R-Enantiomer of N-propargyl-1-aminoindan, salts, compsns. and uses thereof. WO 9511016 .

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)	14861	1-indanamine; 2,3-dihydro-1H-inden-1-ylamine; 1-Aminoindane	34698-41-4	C₉H₁₁N	详情	详情
(II)	14862	Propargyl chloride; 3-chloro-1-propyne	624-65-7	C₃H₃Cl	详情	详情
(III)	14863	(1R)-2,3-Dihydro-1H-inden-1-ylamine; (R)-(-)-1-Aminoindan; (1R)-2,3-Dihydro-1H-inden-1-amine	10277-74-4	C₉H₁₁N	详情	详情
(IV)	14864	N-(1-Indanyl)propargylamine; N-(2,3-dihydro-1H-inden-1-yl)-N-(2-propynyl)amine; N-(2-propynyl)-1-indanamine	1875-50-9	C₁₂H₁₃N	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)