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【结 构 式】 
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【分子编号】10260 【品名】tert-butyl N-(3-hydroxypropyl)carbamate 【CA登记号】58885-58-8 |
【 分 子 式 】C8H17NO3 【 分 子 量 】175.22792 【元素组成】C 54.84% H 9.78% N 7.99% O 27.39% |
合成路线1
该中间体在本合成路线中的序号：(I)The synthesis of racemic 15-deoxyspergualin and tritium-labeled compound has been described: The oxidation of N-(3-hydroxypropyl)carbamic acid tert-butyl ester (I) with pyridinium chlorochromate in dichloromethane gives N-(3-oxopropyl)carbamic acid tert-butyl ester (II), which is condensed with 4-(triphenylphosphonium)butyrate (III) by means of lithium bis(trimethylsilyl)amide in THF yielding 7-(tert-butoxycarbonylamino)-4-heptenoic acid (IV). The esterification of (IV) with N-hydroxysuccinimide (V) by means of dicyclohexylcarbodiimide and 1-hydroxybenzotriazole affords the corresponding ester (VI), which is treated with ammonia in methanol giving the corresponding amide (VII). The hydrolysis of (VII) with HCl in ethyl acetate yields 7-amino-4-heptenamide (VIII), which is treated with 3,5-dimethylpyrazole-1-carboxamidine (IX) and K2CO3 in methanol affording 7-guanidino-4-heptenamide (X). The reduction of (X) gives 7-guanidinoheptanamide (XI), which is finally condensed with glyoxylspermidine (XII) by means of glutaric acid in hot water. The tritium-labeled compound can also be obtained in the same way by performing the reduction of heptenamide (X) with tritium gas.
| 【1】 Cook, D.J.; Tepper, M.A.; Saulnier, M.G.; Dischino, D.D.; Synthesis of tritium labeled (±) 15-deoxyspergualin trihydrochloride. J Label Compd Radiopharm 1993, 33, 2, 137. |
| 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) | 10260 | tert-butyl N-(3-hydroxypropyl)carbamate | 58885-58-8 | C8H17NO3 | 详情 | 详情 |
| (II) | 10261 | tert-butyl N-(3-oxopropyl)carbamate | C8H15NO3 | 详情 | 详情 | |
| (III) | 10262 | 4-(triphenylphosphonio)butanoate | C22H22O2P | 详情 | 详情 | |
| (IV) | 10263 | (E)-7-[(tert-Butoxycarbonyl)amino]-4-heptenoic acid | C12H21NO4 | 详情 | 详情 | |
| (V) | 10264 | 1-Hydroxydihydro-1H-pyrrole-2,5-dione; N-Hydroxysuccinimide; 1-Hydroxy-2,5-pyrrolidinedione | 6066-82-6 | C4H5NO3 | 详情 | 详情 |
| (VI) | 10265 | tert-butyl N-[(E)-7-[(2,5-dioxo-1-pyrrolidinyl)oxy]-7-oxo-3-heptenyl]carbamate | C16H24N2O6 | 详情 | 详情 | |
| (VII) | 10266 | tert-butyl N-[(E)-7-amino-7-oxo-3-heptenyl]carbamate | C12H22N2O3 | 详情 | 详情 | |
| (VIII) | 10267 | (E)-7-Amino-4-heptenamide | C7H14N2O | 详情 | 详情 | |
| (IX) | 10268 | 3,5-Dimethyl-1H-pyrazole-1-carboximidamide | C6H10N4 | 详情 | 详情 | |
| (X) | 10269 | (E)-7-[[Amino(imino)methyl]amino]-4-heptenamide | C8H16N4O | 详情 | 详情 | |
| (XI) | 10270 | 7-[[Amino(imino)methyl]amino]heptanamide | C8H18N4O | 详情 | 详情 | |
| (XI) | 44635 | 7-[[amino(imino)methyl]amino]heptanamide | C8H18N4O | 详情 | 详情 | |
| (XII) | 10271 | N-[4-[(3-Aminopropyl)amino]butyl]-2,2-dihydroxyacetamide | C9H21N3O3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XXI)The precursor aminopropiophenone (XXVII) was synthesized as follows: 3-Amino-1-propanol (XX) was converted to the N-Boc derivative (XXI) and subsequently sulfonylated with p-toluenesulfonyl chloride to afford tosylate (XXII). Addition of vinylmagnesium bromide to 5-hydroxy-2-nitrobenzaldehyde (XXIII) provided the allyl alcohol (XXIV). The phenolic hydroxyl of (XXIV) was then alkylated with tosylate (XXII), yielding ether (XXV). The oxidation of the OH group of (XXV) with MnO2 gave the unsaturated ketone (XXVI). Catalytic hydrogenation of the olefin and nitro groups of (XXVI) provided the aminopropiophenone (XXVII).
| 【1】 Tsujihara, K.; Kawaguchi, T.; Okuno, S.; Yano, T. (Tanabe Seiyaku Co., Ltd.); Camptothecin derivs.. CA 2182244; EP 0757049; JP 1998072467; US 5837673 . |
| 【2】 Nomura, S.; Tsujihara, K.; Kawaguchi, T. (Tanabe Seiyaku Co., Ltd.); S type 2-substd. hydroxy-2-indolidinylbutyric ester cpds. and process for preparation thereof. US 6277992 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XX) | 18522 | 3-amino-1-propanol | 156-87-6 | C3H9NO | 详情 | 详情 |
| (XXI) | 10260 | tert-butyl N-(3-hydroxypropyl)carbamate | 58885-58-8 | C8H17NO3 | 详情 | 详情 |
| (XXII) | 49950 | 3-[(tert-butoxycarbonyl)amino]propyl 4-methylbenzenesulfonate | C15H23NO5S | 详情 | 详情 | |
| (XXIII) | 14942 | 5-hydroxy-2-nitrobenzaldehyde | 42454-06-8 | C7H5NO4 | 详情 | 详情 |
| (XXIV) | 49951 | 3-(1-hydroxy-2-propenyl)-4-nitrophenol | C9H9NO4 | 详情 | 详情 | |
| (XXV) | 49952 | tert-butyl 3-[3-(1-hydroxy-2-propenyl)-4-nitrophenoxy]propylcarbamate | C17H24N2O6 | 详情 | 详情 | |
| (XXVI) | 49953 | tert-butyl 3-(3-acryloyl-4-nitrophenoxy)propylcarbamate | C17H22N2O6 | 详情 | 详情 | |
| (XXVII) | 49954 | tert-butyl 3-(4-amino-3-propionylphenoxy)propylcarbamate | C17H26N2O4 | 详情 | 详情 |