2-(2,3-dihydro-1H-inden-2-yl)acetic acid -Drug Synthesis Database

【结构式】

【分子编号】21721

【品名】2-(2,3-dihydro-1H-inden-2-yl)acetic acid

【CA登记号】37868-26-1

【分子式】C₁₁H₁₂O₂

【分子量】176.21508

【元素组成】C 74.98% H 6.86% O 18.16%

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：(IV)

Aldol condensation between 1-indanone (I) and glyoxylic acid (II) in the presence of H2SO4 afforded keto acid (III). Catalytic hydrogenation of (III) over Pd/C furnished 2-indanylacetic acid (IV).

参考文献中间体

合成目标

【1】 Arai, H.; Niwa, S.; Nishioka, H.; Yamanaka, T.; Torizuka, M.; Yoshinaga, K.; Kobayashi, N.; Ikeda, Y.; Tanaka, Y.; New potent prolyl endopeptidase inhibitors: Synthesis and structure-activity relationships of indan and tetralin derivatives and their analogues. J Med Chem 1994, 37, 13, 2071.

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)	15618	2-Oxoacetic acid; Glyoxylic Acid	298-12-4	C₂H₂O₃	详情	详情
(III)	55611	2-(1-oxo-1,3-dihydro-2H-inden-2-ylidene)acetic acid		C₁₁H₈O₃	详情	详情
(IV)	21721	2-(2,3-dihydro-1H-inden-2-yl)acetic acid	37868-26-1	C₁₁H₁₂O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

Coupling of indanylacetic acid (IV) with L-thioproline ethyl ester (V) by means of EDC gave amide (VI). Subsequent saponification of the ethyl ester group of (VI) furnished (indanylacetyl)thioproline (VII). The title compound was finally obtained by coupling of acid (VII) with pyrrolidine (VIII).

参考文献中间体

合成目标

【1】 Aotsuka, T.; Torizuka, M.; Soeda, M.; Ogura, K.; Tanaka, Y.; Kato, H.; Nakata, N.; Miura, N.; Morita, H. (Zeria Pharmaceutical Co., Ltd.); Condensed benzene deriv.. AU 8945914; EP 0372484; JP 1990262557; US 5028604 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IV)	21721	2-(2,3-dihydro-1H-inden-2-yl)acetic acid	37868-26-1	C₁₁H₁₂O₂	详情	详情
(V)	12901	ethyl (4R)-1,3-thiazolidine-4-carboxylate		C₆H₁₁NO₂S	详情	详情
(VI)	55612	ethyl (4R)-3-[2-(2,3-dihydro-1H-inden-2-yl)acetyl]-1,3-thiazolidine-4-carboxylate		C₁₇H₂₁NO₃S	详情	详情
(VII)	55613	(4R)-3-[2-(2,3-dihydro-1H-inden-2-yl)acetyl]-1,3-thiazolidine-4-carboxylic acid		C₁₅H₁₇NO₃S	详情	详情
(VIII)	11376	Pyrrolidine	123-75-1	C₄H₉N	详情	详情

合成路线3

该中间体在本合成路线中的序号：(IV)

Alternatively, the title compound was prepared by condensation between indanylacetic acid (IV) and thioprolylpyrrolidine (XI) either using EDC as the coupling reagent or via activation as the mixed anhydride (X) with pivaloyl chloride (IX) and triethylamine.

参考文献中间体

合成目标

【1】 Arai, H.; Niwa, S.; Nishioka, H.; Yamanaka, T.; Torizuka, M.; Yoshinaga, K.; Kobayashi, N.; Ikeda, Y.; Tanaka, Y.; New potent prolyl endopeptidase inhibitors: Synthesis and structure-activity relationships of indan and tetralin derivatives and their analogues. J Med Chem 1994, 37, 13, 2071.
【2】 Tanaka, Y.; Kobayashi, N.; Nakata, N.; Yamaguchi, I.; Mori, T. (Zeria Pharmaceutical Co., Ltd.); Cholinesterase activator. EP 0754454; JP 1995228529; US 6017929; WO 9522326 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IV)	21721	2-(2,3-dihydro-1H-inden-2-yl)acetic acid	37868-26-1	C₁₁H₁₂O₂	详情	详情
(IX)	13597	2,2-Dimethylpropanoyl chloride; Pivaloyl chloride	3282-30-2	C₅H₉ClO	详情	详情
(X)	55164	(6aS,12aR)-2,3-dimethoxy-6-propyl-6a,12a-dihydro-5H-[1,3]dioxolo[4',5':5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione		C₂₂H₂₁NO₆	详情	详情
(XI)	55165	(6aS,12R,12aR)-2,3-dimethoxy-6-propyl-6,6a,12,12a-tetrahydro-5H-[1,3]dioxolo[4',5':5,6]indeno[1,2-c]isoquinolin-12-ol		C₂₂H₂₅NO₅	详情	详情

合成路线4

该中间体在本合成路线中的序号：(I)

Curtius rearrangement of indanylacetic acid (I) using diphenylphosphoryl azide (DPPA) in the presence of benzyl alcohol afforded benzyl carbamate (II). Hydrogenolytic deprotection of (II) in the presence of palladium catalyst then provided amine (III), which was condensed with 4-chlorobenzenesulfonyl chloride (IV) to give sulfonamide (V). Subsequent Friedel Crafts reaction of (V) with ethyl a-chloro-a-(methylsulfanyl)acetate (VI) and SnCl4 furnished sulfide (VII), from which the methylthio group was removed by reductive treatment with Zn dust in AcOH yielding (VIII). Finally, alkaline hydrolysis of the indanylacetic ester (VIII) provided the title carboxylic acid, isolated as the corresponding sodium salt.

参考文献中间体

合成目标

【1】 Iwakuma, T.; Kurimoto, T.; Yoshida, K.; Shinozaki, K.; Sato, R.; Sato, H.; Synthesis and thromboxane A2 antagonistic activity of indane derivatives. Bioorg Med Chem Lett 1999, 9, 3, 401.

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)	21721	2-(2,3-dihydro-1H-inden-2-yl)acetic acid	37868-26-1	C₁₁H₁₂O₂	详情	详情
(II)	21722	benzyl 2,3-dihydro-1H-inden-2-ylmethylcarbamate		C₁₈H₁₉NO₂	详情	详情
(III)	21723	2,3-dihydro-1H-inden-2-ylmethylamine; 2,3-dihydro-1H-inden-2-ylmethanamine		C₁₀H₁₃N	详情	详情
(IV)	15787	4-chlorobenzenesulfonyl chloride;4-chlorobenzene-1-sulfonyl chloride	98-60-2	C₆H₄Cl₂O₂S	详情	详情
(V)	21725	4-chloro-N-(2,3-dihydro-1H-inden-2-ylmethyl)benzenesulfonamide		C₁₆H₁₆ClNO₂S	详情	详情
(VI)	21726	ethyl 2-chloro-2-(methylsulfanyl)acetate		C₅H₉ClO₂S	详情	详情
(VII)	21727	ethyl 2-[2-([[(4-chlorophenyl)sulfonyl]amino]methyl)-2,3-dihydro-1H-inden-5-yl]-2-(methylsulfanyl)acetate		C₂₁H₂₄ClNO₄S₂	详情	详情
(VIII)	21728	ethyl 2-[2-([[(4-chlorophenyl)sulfonyl]amino]methyl)-2,3-dihydro-1H-inden-5-yl]acetate		C₂₀H₂₂ClNO₄S	详情	详情

Extended Information