(1R)-2,3-Dihydro-1H-inden-1-ylamine; (R)-(-)-1-Aminoindan; (1R)-2,3-Dihydro-1H-inden-1-amine -Drug Synthesis Database

【结构式】

【分子编号】14863

【品名】(1R)-2,3-Dihydro-1H-inden-1-ylamine; (R)-(-)-1-Aminoindan; (1R)-2,3-Dihydro-1H-inden-1-amine

【CA登记号】10277-74-4

【分子式】C₉H₁₁N

【分子量】133.19308

【元素组成】C 81.16% H 8.32% N 10.52%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(III)

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

合成目标

【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

合成路线2

该中间体在本合成路线中的序号：(I)

Treatment of (R)-1-aminoindan (I) with trifluoroacetic anhydride in toluene affords trifluoroacetyl derivative (II), which is condensed with chloroacetyl chloride (III) by means of AlCl3 in 1,2-dichloroethane to provide compound (IV). Oxidation of chloroacetyl derivative (IV) with 3-chloroperoxybenzoic acid (mCPBA) and TFA in CH2Cl2 allows formation of chloroacetoxy (V), which is converted into the hydroxy form (VI) by heating in hot methanol/H2O in the presence of K2CO3. N-Protection of (VI) is then performed by treatment with di-t-butyl dicarbonate and Et3N in THF to furnish Boc derivative (VII), which is then converted into derivative (IX) by O-acylation with N-Me, N-Et carbamoyl chloride (VIII) by means of NaH in acetonitrile. Removal of the Boc group of (IX) by treatment with HCl (gas) in dioxane gives hydrochloride (X), which is finally N-alkylated with propargyl bromide (XI) by means of K2CO3 in acetonitrile to yield the desired product.

参考文献中间体

合成目标

【1】 Youdim, M.B.H.; Herzig, Y.; Sterling, J.; Goren, T.; Chorev, M. (Technion - Israel Institute of Technology; Teva Pharmaceutical Industries Ltd.; Yissum Research Development Co.); Aminoindan derivs.. EP 0966435; JP 2001506269; WO 9827055 .

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)	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
(II)	46687	N-[(1R)-2,3-dihydro-1H-inden-1-yl]-2,2,2-trifluoroacetamide		C₁₁H₁₀F₃NO	详情	详情
(III)	11296	2-Chloroacetyl chloride; Chloroacetic chloride	79-04-9	C₂H₂Cl₂O	详情	详情
(IV)	46688	N-[(1R)-6-(2-chloroacetyl)-2,3-dihydro-1H-inden-1-yl]-2,2,2-trifluoroacetamide		C₁₃H₁₁ClF₃NO₂	详情	详情
(V)	46689	(3R)-3-[(2,2,2-trifluoroacetyl)amino]-2,3-dihydro-1H-inden-5-yl 1lambda(3)-dichlorane-1-carboxylate		C₁₂H₁₀Cl₂F₃NO₃	详情	详情
(VI)	46690	(3R)-3-amino-2,3-dihydro-1H-inden-5-ol		C₉H₁₁NO	详情	详情
(VII)	46691	tert-butyl (1R)-6-hydroxy-2,3-dihydro-1H-inden-1-ylcarbamate		C₁₄H₁₉NO₃	详情	详情
(VIII)	46692	1,2-dimethyl-1-hydrazinecarbonyl chloride		C₃H₇ClN₂O	详情	详情
(IX)	46693	(3R)-3-[(tert-butoxycarbonyl)amino]-2,3-dihydro-1H-inden-5-yl 1,2-dimethyl-1-hydrazinecarboxylate		C₁₇H₂₅N₃O₄	详情	详情
(X)	46694	(3R)-3-amino-2,3-dihydro-1H-inden-5-yl 1,2-dimethyl-1-hydrazinecarboxylate		C₁₂H₁₇N₃O₂	详情	详情
(XI)	11176	3-Bromopropyne; 3-Bromo-1-propyne	106-96-7	C₃H₃Br	详情	详情

Extended Information