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【结 构 式】 
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【分子编号】29020 【品名】2-bromo-N-(2-bromoethyl)-1-ethanamine 【CA登记号】 |
【 分 子 式 】C4H9Br2N 【 分 子 量 】230.9302 【元素组成】C 20.8% H 3.93% Br 69.2% N 6.07% |
合成路线1
该中间体在本合成路线中的序号：(B)OPC-8212 is obtained through the piperazine ring formation method from bis(beta-bromoethyl)amine hydrobromide and 6-amino-3,4-dihydro-2(1H)-quinolinone (V) to give (VI). (V) is synthesized using the ring closure reaction of p-acetylamino-beta-ethoxyacryloanilide (II). p-Acetylaminoaniline (I) is converted to (II) by treatment with beta-ethoxyacryloyl chloride and afterwards cyclized in the presence of sulfuric acid to give 6-acetylamino-2-(1H)-quinolinone (III). Hydrogenation of (III) over 10% palladium on charcoal gives 6-acetylamino-3,4-dihydro-2(1H)-quinolinone (IV). Hydrolysis of (IV) gives 6-amino-3,4-dihydro-2(1H)-quinolinone (V). OPC-8212 is obtained by adding 3,4-dimethoxybenzyl chloride (VII) to (VI).
| 【1】 Nakagawa, K.; Osumi, T.; Shimizu, T.; Niimi, K.; Physicochemical properties and stabilities of a new positive inotropic agent, OPC 8212. Arzneim-Forsch Drug Res 1984, 34, 3A, 334-341. |
| 【2】 Yo, E.; Ogawa, H.; Yamashita, S.; Tominaga, M.; Nakagawa, K.; Yabuuchi, Y.; Studies on positive inotropic agents. I. Synthesis of 3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-2(1H)-quinolinone and related compounds. Chem Pharm Bull 1984, 32, 6, 2100. |
| 【3】 Mannhold, R.; OPC-8212. Drugs Fut 1985, 10, 1, 28. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 20616 | (E)-3-ethoxy-2-propenoyl chloride | 99471-66-6 | C5H7ClO2 | 详情 | 详情 |
| (B) | 29020 | 2-bromo-N-(2-bromoethyl)-1-ethanamine | C4H9Br2N | 详情 | 详情 | |
| (I) | 29016 | N-(4-aminophenyl)acetamide | 122-80-5 | C8H10N2O | 详情 | 详情 |
| (II) | 29017 | (E)-N-[4-(acetamido)phenyl]-3-ethoxy-2-propenamide | C13H16N2O3 | 详情 | 详情 | |
| (III) | 29018 | N-(2-oxo-1,2-dihydro-6-quinolinyl)acetamide | C11H10N2O2 | 详情 | 详情 | |
| (IV) | 29019 | N-(2-oxo-1,2,3,4-tetrahydro-6-quinolinyl)acetamide | C11H12N2O2 | 详情 | 详情 | |
| (V) | 29022 | 6-amino-3,4-dihydro-2(1H)-quinolinone | C9H10N2O | 详情 | 详情 | |
| (VI) | 29021 | 6-(1-piperazinyl)-3,4-dihydro-2(1H)-quinolinone | C13H17N3O | 详情 | 详情 | |
| (VII) | 13438 | 3,4-Dimethoxybenzoyl chloride | 3535-37-3 | C9H9ClO3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(III)Reduction of 5-nitro-2-furaldehyde (I) with NaBH4 provided the corresponding alcohol (II). The phosphoramidic dichloride (IV) was prepared by treatment of bis(2-bromoethyl)amine (III) with phosphorus oxychloride in the presence of triethylamine at -40 C. Condensation of acid chloride (IV) with the lithium alkoxide of (II) at -78 C produced the intermediate (V), which was treated in situ with gaseous ammonia at -20 C, yielding the title phosphorodiamidate.
| 【1】 Joswig, C.; Marakovits, J.T.; Liu, J.; Mulcahy, R.T.; Borch, R.F.; Schmidt, J.P.; Gipp, J.J.; Synthesis and evaluation of nitroheterocyclic phosphoramidates as hypoxia-selective alkylating agents. J Med Chem 2000, 43, 11, 2258. |