5,6-Dimethoxy-1-indanone; 2,3-Dihydro-5,6-dimethoxy-1H-inden-1-one -Drug Synthesis Database

【结构式】

【分子编号】13430

【品名】5,6-Dimethoxy-1-indanone; 2,3-Dihydro-5,6-dimethoxy-1H-inden-1-one

【CA登记号】2107-69-9

【分子式】C₁₁H₁₂O₃

【分子量】192.21448

【元素组成】C 68.74% H 6.29% O 24.97%

与该中间体有关的原料药合成路线共 4 条

合成路线1 合成路线2 合成路线3 合成路线4

合成路线1

该中间体在本合成路线中的序号：(I)

The condensation of 5,6-dimethoxy-1-indanone (I) with 1-benzylpiperidine-4-carboxaldehyde (II) by means of butyllithium and diisopropylamine in THF gives 1-benzyl-4-(5,6-dimethoxy-1-oxoindan-2-ylidenemethyl)piperidine (III), which is reduced with H2 over Pd/C in THF and treated with HCl in dichloromethane - ethyl acetate.

参考文献中间体

合成目标

【1】 Sugimoto, H.; Tsuchiya, Y.; Higurashi, K.; Karibe, N.; Iimura, Y.; Sasaki, A.; Yamanashi, Y.; Ogura, H.; Araki, S.; Kosasa, T.; Kusota, A.; Kozasa, M.; Yamatsu, K. (Eisai Co., Ltd.); Cyclic amine cpd., its use and pharmaceutical compsns. comprising it. AU 8818216; EP 0296560; EP 0673927; EP 0742207; JP 1989079151; JP 1998067739; US 4895841; US 5100901 .
【2】 Sugimoto, H.; Mishima, M.; Iimura, Y.; Synthesis of 1-benzyl-4-[(5,6-dimethoxy[2-14C]-1-indanon)-2-yl]methylpiperidine hydrochloride (E-2020-14C). J Label Compd Radiopharm 1989, 27, 7, 835-9.
【3】 Castaner, J.; Prous, J.; E-2020. Drugs Fut 1991, 16, 1, 16.

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)	13430	5,6-Dimethoxy-1-indanone; 2,3-Dihydro-5,6-dimethoxy-1H-inden-1-one	2107-69-9	C₁₁H₁₂O₃	详情	详情
(II)	13431	1-Benzyl-4-piperidinecarbaldehyde		C₁₃H₁₇NO	详情	详情
(III)	13432	2-[(E)-(1-Benzyl-4-piperidinyl)methylidene]-5,6-dimethoxy-1-indanone	120014-07-5	C₂₄H₂₇NO₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Nitrosation of 5,6-dimethoxy-1-indanone (I) with n-butyl nitrite and HCl in MeOH at 40 C provided oxime (II). Subsequent catalytic hydrogenation of ketone and oxime groups of (II) afforded the 2-aminoindan (III). Reductive alkylation of (III) using propionic acid and NaBH4 then gave the target dipropylamino compound, which was isolated as the hydrochloride salt after separation of some unreacted material by treatment with phenyl isocyanate.

参考文献中间体

合成目标

【1】 Cannon, J.G.; et al.; Conformationally restricted congeners of dopamine derived from 2-aminoindan. J Med Chem 1982, 25, 12, 1442.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	20178	propionic acid	79-09-4	C₃H₆O₂	详情	详情
	31340	butyl nitrite	544-16-1	C₄H₉NO₂	详情	详情
(I)	13430	5,6-Dimethoxy-1-indanone; 2,3-Dihydro-5,6-dimethoxy-1H-inden-1-one	2107-69-9	C₁₁H₁₂O₃	详情	详情
(II)	27302	5,6-dimethoxy-1H-indene-1,2(3H)-dione 2-oxime		C₁₁H₁₁NO₄	详情	详情
(III)	27303	5,6-dimethoxy-2,3-dihydro-1H-inden-2-ylamine		C₁₁H₁₅NO₂	详情	详情

合成路线3

该中间体在本合成路线中的序号：(V)

Knoevenagel condensation of 3,4-dimethoxybenzaldehyde (I) with malonic acid produced the cinnamic acid (II), which was further reduced to (III) by catalytic hydrogenation using Pd/C. Conversion of (III) to the corresponding acid chloride (IV), followed by Friedel-Crafts intramolecular cyclization gave the indanone (V). Nitrosation of (V) yielded the oximino derivative (VI), which was subsequently silylated with t-butyldimethylsilyl chloride and imidazole to afford the O-silyl oxime (VII). Reduction of (VII) with borane-dimethyl sulfide complex produced the amino alcohol (VIII). Without isolation, (VIII) was converted to the dipropylamino compound (IX) by reductive alkylation with propionaldehyde and NaBH(OAc)3. Amino alcohol (IX) was finally deoxygenated by means of triethylsilane in the presence of boron trifluoride etherate.

参考文献中间体

合成目标

【1】 Haadsma-Svensson, S.R.; Cleek, K.A.; Dinh, D.M.; et al.; Dopamine D3 receptor antagonists. 1. Synthesis and structure-activity relationships of 5,6-dimethoxy-N-alkyl- and N-alkylaryl-substituted 2-aminoindans. J Med Chem 2001, 44, 26, 4716.

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)	18304	3,4-Dimethoxybenzaldehyde; Veratraldehyde	120-14-9	C₉H₁₀O₃	详情	详情
(II)	28568	(E)-3-(3,4-dimethoxyphenyl)-2-propenoic acid	2316-26-9	C₁₁H₁₂O₄	详情	详情
(III)	40182	3-(3,4-dimethoxyphenyl)propionic acid	2107-70-2	C₁₁H₁₄O₄	详情	详情
(IV)	56565	3-(3,4-dimethoxyphenyl)propanoyl chloride		C₁₁H₁₃ClO₃	详情	详情
(V)	13430	5,6-Dimethoxy-1-indanone; 2,3-Dihydro-5,6-dimethoxy-1H-inden-1-one	2107-69-9	C₁₁H₁₂O₃	详情	详情
(VI)	27302	5,6-dimethoxy-1H-indene-1,2(3H)-dione 2-oxime		C₁₁H₁₁NO₄	详情	详情
(VII)	56566	5,6-dimethoxy-1H-indene-1,2(3H)-dione 2-{O-[tert-butyl(dimethyl)silyl]oxime}		C₁₇H₂₅NO₄Si	详情	详情
(VIII)	56567	2-amino-5,6-dimethoxy-1-indanol		C₁₁H₁₅NO₃	详情	详情
(IX)	56568	2-(dipropylamino)-5,6-dimethoxy-1-indanol		C₁₇H₂₇NO₃	详情	详情

合成路线4

该中间体在本合成路线中的序号：(I)

5,6-Dimethoxy-1-indanone (I) was selectively nitrated at position 7 by means of NaNO2 in trifluoroacetic acid. Acid-catalyzed aldol condensation of the resulting nitroindanone (II) with 3,5-dimethyl-4-hydroxybenzaldehyde (III) afforded the E-unsaturated ketone (IV). Finally, reduction of the nitro group of (IV) with either sodium dithionite or zinc dust and AcOH yielded the corresponding amino derivative.

参考文献中间体

合成目标

【1】 Shih, H.; Carson, D.A.; Deng, L.; Carrer, C.J.; Cottam, H.B.; Adachi, C.J.; Rational design, synthesis and structure-activity relationships of antitumor (E)-2-benzylidene-1-tetralones and (E)-2-benzylidene-1-indanones. Bioorg Med Chem Lett 2000, 10, 5, 487.

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)	13430	5,6-Dimethoxy-1-indanone; 2,3-Dihydro-5,6-dimethoxy-1H-inden-1-one	2107-69-9	C₁₁H₁₂O₃	详情	详情
(II)	39984	5,6-dimethoxy-7-nitro-1-indanone		C₁₁H₁₁NO₅	详情	详情
(III)	39985	4-hydroxy-3,5-dimethylbenzaldehyde；3,5-Dimethyl-4-hydroxybenzaldehyde	2233-18-3	C₉H₁₀O₂	详情	详情
(IV)	39986	2-[(E)-(4-hydroxy-3,5-dimethylphenyl)methylidene]-5,6-dimethoxy-7-nitro-1-indanone		C₂₀H₁₉NO₆	详情	详情

Extended Information