【结 构 式】 |
【药物名称】DN-1417 【化学名称】gamma-Butyrolactone-gamma-carbonylhistidylprolinamide citrate 【CA登记号】63836-94-2 ((S)-isomer) 【 分 子 式 】C22H29N5O12 【 分 子 量 】555.50273 |
【开发单位】Takeda (Originator) 【药理作用】Adjuncts to Anesthesia, ANALGESIC AND ANESTHETIC DRUGS, Antiepileptic Drugs, NEUROLOGIC DRUGS, Respiratory Stimulants, TRH Analogs |
合成路线1
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 |