【结 构 式】 |
【分子编号】30550 【品名】1,3-dihydro-2H-inden-2-one 【CA登记号】615-13-4 |
【 分 子 式 】C9H8O 【 分 子 量 】132.16192 【元素组成】C 81.79% H 6.1% O 12.11% |
合成路线1
该中间体在本合成路线中的序号:(II)The reductocondensation of ethyl glycinate (I) with 2-indanone (II) by means of sodium cyanoborohydride in methanol gives ethyl N-(2-indanyl)glycinate (III), which is condensed with N-benzyloxycarbonyl-L-alanine (IV) by means of isobutyl chlorocarbonate and triethylamine in THF yielding N-(N-benzyloxycarbonyl-L-alanyl)-N-(2-indanyl)glycine ethyl ester (V). The partial hydrolysis of (V) with NaOH in methanol affords N-(N-benzyloxycarbonyl-L-alanyl)-N-(2-indanyl)glycine (VI), which is deprotected by hydrogenolysis with H2 over Pd/C in ethanol giving N-(L-alanyl)-N-(2-indanyl)glycine (VII). Finally, this compound is reductocondensed with ethyl 2-oxo-4-phenylbutanoate (VIII) by means of sodium cyanoborohydride in ethanol.
【1】 Oka, Y.; Nishikawa, K.; Miyake, A. (Takeda Chemical Industries, Ltd.); Bicyclic compounds, their production and use. EP 0051391; GB 2086393; JP 82179141; JP 8277651; US 4385051 . |
【2】 Serradell, M.N.; Castaner, J.; CV-3317. Drugs Fut 1984, 9, 5, 324. |
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) | 10309 | ethyl 2-aminoacetate; Glycine ethyl ester | 459-73-4 | C4H9NO2 | 详情 | 详情 |
(II) | 30550 | 1,3-dihydro-2H-inden-2-one | 615-13-4 | C9H8O | 详情 | 详情 |
(III) | 30551 | ethyl 2-(2,3-dihydro-1H-inden-2-ylamino)acetate | C13H17NO2 | 详情 | 详情 | |
(IV) | 61209 | CBZ-L-Alanine; (2S)-2-[[(Benzyloxy)carbonyl]amino]propionic acid; N-((Phenylmethoxy)carbonyl)-alanine; Carbobenzyloxy-L-alanine | C11H13NO4 | 详情 | 详情 | |
(V) | 30552 | ethyl 2-[((2S)-2-[[(benzyloxy)carbonyl]amino]propanoyl)(2,3-dihydro-1H-inden-2-yl)amino]acetate | C24H28N2O5 | 详情 | 详情 | |
(VI) | 30553 | 2-[((2S)-2-[[(benzyloxy)carbonyl]amino]propanoyl)(2,3-dihydro-1H-inden-2-yl)amino]acetic acid | C22H24N2O5 | 详情 | 详情 | |
(VII) | 30554 | 2-[[(2S)-2-aminopropanoyl](2,3-dihydro-1H-inden-2-yl)amino]acetic acid | C14H18N2O3 | 详情 | 详情 | |
(VIII) | 20896 | Ethyl 2-oxo-4-phenylbutanoate; 2-Oxo-4-phenylbutyric acid ethyl ester | 64920-29-2 | C12H14O3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号:(II)The reductocondensation of (II) with tert-butyl glycinate (IX) by means of sodium cyanoborohydride in ethanol gives tert-butyl-N-(2-indanyl)glycinate (X), which is condensed with (IV) by means of isobutyl chlorocarbonate as before yielding tert-butyl-N-[N-(tert-butoxycarbonyl)-L-alanyl]-N-(2-indanyl)glycinate (XI). Deprotection of (XI) by hydrogenolysis with H2 over Pd/C in methanol affords tert-butyl N-(L-alanyl)-N-(2-indanyl)glycinate (XII), which is reductocondensed with (VIII) using H2 and Raney-Ni in ethanol to afford tert-butyl N-[N-(1-ethoxycarbonyl-3-phenylpropyl)-L-alanyl]-N-(2-indanyl)glycinate (XIII). Finally, this compound is saponified with HBr in acetic acid.
【1】 Oka, Y.; Nishikawa, K.; Miyake, A. (Takeda Chemical Industries, Ltd.); Bicyclic compounds, their production and use. EP 0051391; GB 2086393; JP 82179141; JP 8277651; US 4385051 . |
【2】 Serradell, M.N.; Castaner, J.; CV-3317. Drugs Fut 1984, 9, 5, 324. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(II) | 30550 | 1,3-dihydro-2H-inden-2-one | 615-13-4 | C9H8O | 详情 | 详情 |
(IV) | 61209 | CBZ-L-Alanine; (2S)-2-[[(Benzyloxy)carbonyl]amino]propionic acid; N-((Phenylmethoxy)carbonyl)-alanine; Carbobenzyloxy-L-alanine | C11H13NO4 | 详情 | 详情 | |
(VIII) | 20896 | Ethyl 2-oxo-4-phenylbutanoate; 2-Oxo-4-phenylbutyric acid ethyl ester | 64920-29-2 | C12H14O3 | 详情 | 详情 |
(IX) | 27841 | tert-butyl 2-aminoacetate;tert-butyl glycinate;Glycine tert-butyl ester | 6456-74-2 | C6H13NO2 | 详情 | 详情 |
(X) | 30555 | tert-butyl 2-(2,3-dihydro-1H-inden-2-ylamino)acetate | C15H21NO2 | 详情 | 详情 | |
(XI) | 30556 | tert-butyl 2-[((2S)-2-[[(benzyloxy)carbonyl]amino]propanoyl)(2,3-dihydro-1H-inden-2-yl)amino]acetate | C26H32N2O5 | 详情 | 详情 | |
(XII) | 30557 | tert-butyl 2-[[(2S)-2-aminopropanoyl](2,3-dihydro-1H-inden-2-yl)amino]acetate | C18H26N2O3 | 详情 | 详情 | |
(XIII) | 30558 | ethyl (2S)-2-([(1S)-2-[[2-(tert-butoxy)-2-oxoethyl](2,3-dihydro-1H-inden-2-yl)amino]-1-methyl-2-oxoethyl]amino)-4-phenylbutanoate | C30H40N2O5 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号:(I)The reductive condensation between 2-indanone (I) and glycine methyl ester (II) in the presence of sodium cyanoborohydride furnished methyl (2-indanylamino)acetate (III). Subsequent ammonolysis of the methyl ester group of (III) in methanolic ammonia gave the glycinamide derivative (IV), which was finally converted to the title hydrochloride salt.
【1】 Chiesi, P.; Ventura, P.; Delcanale, M.; De Fanti, R.; Armani, E.; Villetti, G.; Pietra, C. (Chiesi Farmaceutici SpA); alpha-Amino acid amides, preparation thereof and the therapeutical use thereof. EP 0951465; JP 2001506577; US 6114391; WO 9803472 . |