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【结 构 式】 
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【分子编号】13370 【品名】1,3-Dibromobenzene 【CA登记号】108-36-1 |
【 分 子 式 】C6H4Br2 【 分 子 量 】235.90576 【元素组成】C 30.55% H 1.71% Br 67.74% |
合成路线1
该中间体在本合成路线中的序号：(XVII)3) Synthesis of [3H]-labeled CI-980: The reaction of butyllithium with m-dibromobenene (XVII) in ether gives the monolithium derivative (XVIII), which is condensed with N-(ethoxycarbonyl)-L-alanine (VII) yielding the carbamate (XIX). The reduction of (XIX) with NaBH4 in methanol affords the hydroxylated carbamate (XX), which is treated with NaOH in methanol to give the aminoalcohol (XXI). The condensation of N-(2-amino-4-chloro-3-nitropyridin-6-yl)carbamic acid ethyl ester (I) with 2(S)-amino-1-(3-bromophenyl)-1-propanol (XXI) by means of triethylamine in refluxing ethanol gives N-[2-amino-4-[2-(3-bromophenyl)-2-hydroxy-1(S)-methylethylamino]-3-nitropyridin-6-yl]carbamic acid ethyl ester (XXII), which is oxidized with CrO3-pyridine in dichloromethane yielding the corresponding ketone (XXIII). The reductocyclization of (XXIII) with Fe and acetic acid affords the 3-bromo analogue of CI-980 (XXIV), which is finally hydrogenated with 3H2 over Pd/C in THF, and treated with 2-hydroxyethanesulfonic acid in methanol.
| 【1】 Graul, A.; Martell, A.M.; Castaner, J.; Mivobulin Isethionate. Drugs Fut 1997, 22, 9, 980. |
| 【2】 Lee, H.T.; Woo, P.W.K.; Synthesis of [3H]CI-980, ethyl[5-amino-1,2-dihydro-2(S)-methyl-3(3-[3H]phenyl)pyrido[3,4-b] pyrazin-7-yl]carbamate isethionate salt, a tubulin-binding, antimitotic, broad-spectrum antitumor agent. J Label Compd Radiopharm 1994, 34, 1, 11-16. |
| 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) | 13354 | ethyl 6-amino-4-chloro-5-nitro-2-pyridinylcarbamate | C8H9ClN4O4 | 详情 | 详情 | |
| (VI) | 13359 | 2-Hydroxy-1-ethanesulfonic acid | 107-36-8 | C2H6O4S | 详情 | 详情 |
| (VII) | 13360 | (2S)-2-[(Ethoxycarbonyl)amino]propionic acid | C6H11NO4 | 详情 | 详情 | |
| (XVII) | 13370 | 1,3-Dibromobenzene | 108-36-1 | C6H4Br2 | 详情 | 详情 |
| (XVIII) | 13371 | (3-Bromophenyl)lithium | C6H4BrLi | 详情 | 详情 | |
| (XIX) | 13372 | ethyl (1S)-2-(3-bromophenyl)-1-methyl-2-oxoethylcarbamate | C12H14BrNO3 | 详情 | 详情 | |
| (XX) | 13373 | ethyl (1S)-2-(3-bromophenyl)-2-hydroxy-1-methylethylcarbamate | C12H16BrNO3 | 详情 | 详情 | |
| (XXI) | 13374 | (2S)-2-Amino-1-(3-bromophenyl)-1-propanol | C9H12BrNO | 详情 | 详情 | |
| (XXII) | 13375 | ethyl 6-amino-4-[[(1S)-2-(3-bromophenyl)-2-hydroxy-1-methylethyl]amino]-5-nitro-2-pyridinylcarbamate | C17H20BrN5O5 | 详情 | 详情 | |
| (XXIII) | 13376 | ethyl 6-amino-4-[[(1S)-2-(3-bromophenyl)-1-methyl-2-oxoethyl]amino]-5-nitro-2-pyridinylcarbamate | C17H18BrN5O5 | 详情 | 详情 | |
| (XXIV) | 13377 | ethyl (2S)-5-amino-3-(3-bromophenyl)-2-methyl-1,2-dihydropyrido[3,4-b]pyrazin-7-ylcarbamate | C17H18BrN5O2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)The reaction of 1,3-dibromobenzene (I) with trimethylsilyl chloride (II) by means of Mg in ethyl ether gives 3-(trimethylsilyl)bromobenzene (III), which is then condensed with ethyl trifluoroacetate (IV) by means of butyllithium in ethyl ether - hexane.
| 【1】 Schirlin, D.; Collard, J.-N.; Hornsperger, J.-M. (Merrell Pharmaceuticals, Inc.); Novel acetylcholinesterase inhibitors. EP 0403713; EP 0409676; JP 1991038591; US 5693668 . |
| 【2】 Prous, J.; Graul, A.; Castaner, J.; Subreum. Drugs Fut 1994, 19, 9, 845. |