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【结 构 式】 
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【分子编号】36139 【品名】benzyl (1S)-2-[(2S)-2-(aminocarbonyl)pyrrolidinyl]-1-(1H-imidazol-5-ylmethyl)-2-oxoethylcarbamate 【CA登记号】 |
【 分 子 式 】C19H23N5O4 【 分 子 量 】385.42292 【元素组成】C 59.21% H 6.01% N 18.17% O 16.6% |
合成路线1
该中间体在本合成路线中的序号：(IV)The reduction of N-benzyloxycarbonylprolinamide (I) with H2 over Pd/c in methanol gives prolinamide (II), which is condensed with N-benzyloxycarbonylhistidyl hydrazide (III) by means of NaNO2 - HCl in ethyl acetate yielding N-benzyloxycarbonylhistidylprolinamide (IV), The hydrolysis of (IV) with HBr in acetic acid affords histidylprolinamide (V), which is finally condensed with gamma-carboxy-gamma-butyrolactone (VI) by means of pentachlorophenol and dicyclohexylcarbodiimide in DMF. Compound (VI) is prepared by reaction of alpha-aminoglutaric acid (VII) with NaNO2 and 2N H2SO4 in water.
| 【1】 Fujino, M.; Nishimura, P.; Nagawa, Y.; Fukuda, N.; US 4100152 . |
| 【2】 Bauce, L.G.; Goren, H.J.; Synthesis of a series of residue 1-(pyroglutamic acid) analogs of thyrotropin releasing hormone. Intl J Pept Protein Res 1979, 14, 3, 216-226. |
| 【3】 Larsen, S.D.; Stephenson, G.A.; Bunnell, C.A.; Reutzel, S.M.; Nichols, J.R. (Eli Lilly and Company); Intermediates and process for preparing olanzapine. US 6020487 . |
| 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) | 37076 | benzyl (2R)-2-(aminocarbonyl)-1-pyrrolidinecarboxylate | C13H16N2O3 | 详情 | 详情 | |
| (II) | 37077 | (2R)-2-pyrrolidinecarboxamide | C5H10N2O | 详情 | 详情 | |
| (III) | 36138 | benzyl (1S)-2-hydrazino-1-(1H-imidazol-5-ylmethyl)-2-oxoethylcarbamate | 49706-31-2 | C14H17N5O3 | 详情 | 详情 |
| (IV) | 36139 | benzyl (1S)-2-[(2S)-2-(aminocarbonyl)pyrrolidinyl]-1-(1H-imidazol-5-ylmethyl)-2-oxoethylcarbamate | C19H23N5O4 | 详情 | 详情 | |
| (V) | 31253 | (2S)-1-[(2S)-2-amino-3-(1H-imidazol-5-yl)propanoyl]-2-pyrrolidinecarboxamide | C11H17N5O2 | 详情 | 详情 | |
| (VI) | 37075 | 5-oxotetrahydro-2-furancarboxylic acid | C5H6O4 | 详情 | 详情 | |
| (VII) | 28752 | DL-2-Amino propane dicarboxylic acid; DL-2-Aminopentanoic acid; glutamic acid; DL-glutamic acid; (+/-)-2-Aminoglutaric acid | 617-65-2 | C5H9NO4 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IV)The synthesis of thyrotropin releasing hormone (TRH) analogues is described as follows: The reduction of N-benzyloxycarbonylprolinamide (I) with H2 over Pd/C in methanol gives prolinamide (II), which is condensed with N-benzyloxy-carbonylhistidyl hydrazide (III) by means of NaNO2 - HCl in ethyl acetate yielding N-benzyloxycarbonylhistidylprolinamide (IV). The hydrolysis of (IV) with HBr in acetic acid affords histidylprolinamide (V), which is finally condensed with 6-methyl-5-oxothiomorpholinyl-3-carboxylic acid (VI) by means of 1-hydroxybenzotriazole, dicyclohexylcarbodiimide and triethylamine in DMF.
| 【1】 US 4045556 . |
| 【2】 Goren, H.J.; Bauce, L.G.; Synthesis of a series of residue 1-(pyroglutamic acid) analogs of thyrotropin releasing hormone. Intl J Pept Protein Res 1979, 14, 216-226. |
| 【3】 Pento, J.T.; CG-3703. Drugs Fut 1983, 8, 12, 1007. |
| 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) | 36136 | benzyl (2S)-2-(aminocarbonyl)-1-pyrrolidinecarboxylate | 34079-31-7 | C13H16N2O3 | 详情 | 详情 |
| (II) | 36137 | (2S)-2-pyrrolidinecarboxamide;L-prolinamide | 7531-52-4 | C5H10N2O | 详情 | 详情 |
| (III) | 36138 | benzyl (1S)-2-hydrazino-1-(1H-imidazol-5-ylmethyl)-2-oxoethylcarbamate | 49706-31-2 | C14H17N5O3 | 详情 | 详情 |
| (IV) | 36139 | benzyl (1S)-2-[(2S)-2-(aminocarbonyl)pyrrolidinyl]-1-(1H-imidazol-5-ylmethyl)-2-oxoethylcarbamate | C19H23N5O4 | 详情 | 详情 | |
| (V) | 31253 | (2S)-1-[(2S)-2-amino-3-(1H-imidazol-5-yl)propanoyl]-2-pyrrolidinecarboxamide | C11H17N5O2 | 详情 | 详情 | |
| (VI) | 36140 | (3R,6R)-6-methyl-5-oxo-3-thiomorpholinecarboxylic acid | C6H9NO3S | 详情 | 详情 |