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【结 构 式】 
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【分子编号】22523 【品名】1-nitrobenzene 【CA登记号】28250-14-8 |
【 分 子 式 】C6H5NO2 【 分 子 量 】123.11124 【元素组成】C 58.54% H 4.09% N 11.38% O 25.99% |
合成路线1
该中间体在本合成路线中的序号：(X)A synthesis of [14C]-labeled SR-57746A has been described: The iodination of [14C6]-benzene (I) with nitric acid/I2 gives iodobenzene (II), which is treated with sodium trifluoroacetate and CuI yielding trifluoromethylbenzene (III). The nitration of (III) with sodium nitrate affords 3-(trifluoromethyl)nitrobenzene (IV), which is reduced with Fe/HCl to the corresponding aniline (V). The reaction of (V) with tert-butyl nitrite and CuBr2 provides 3-(trifluoromethyl)bromobenzene (VI), which is treated with Mg in THF affording the corresponding Grignard reagent (VII). The condensation of (VII) with piperidone (VIII) gives the piperidol (IX), which is finally dehydrated in acidic medium. In order to aviod radioactive contamination during the purification of compounds iodobenzene (II) and trifluoromethylbenzene (III) by liquid chromatography, a safer route using less volatile compounds has been developed: The nitration of [14C6]-benzene (I) with nitric acid gives nitrobenzene (X), which is iodinated with IPy2BF4/CF3SO3H yielding 3-iodonitrobenzene (XI). Finally, this compound is trifluoromethylated with CF3SiMe3, CuI and KF to provide 3-(trifluoromethyl)nitrobenzene (IV) already reported.
| 【1】 Robic, N.; Noel, J.P.; Synthesis of [trifluoromethyl-[C-14(6)]-phenyl] SR 57746A. J Label Compd Radiopharm 1999, 42, 2, 109. |
| 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) | 13364 | Benzene | 71-43-2 | C6H6 | 详情 | 详情 |
| (I) | 45201 | benzene | C6H6 | 详情 | 详情 | |
| (II) | 26344 | 1-Iodobenzene | 591-50-4 | C6H5I | 详情 | 详情 |
| (II) | 45202 | 1-iodobenzene | C6H5I | 详情 | 详情 | |
| (III) | 26345 | 1-(Trifluoromethyl)benzene | 98-08-8 | C7H5F3 | 详情 | 详情 |
| (III) | 45203 | 1-(trifluoromethyl)benzene | C7H5F3 | 详情 | 详情 | |
| (IV) | 26346 | 1-nitro-3-(trifluoromethyl)benzene | 98-46-4 | C7H4F3NO2 | 详情 | 详情 |
| (IV) | 45204 | 1-nitro-3-(trifluoromethyl)benzene | C7H4F3NO2 | 详情 | 详情 | |
| (V) | 26347 | 3-(trifluoromethyl)phenylamine; 3-(trifluoromethyl)aniline; 3-aminobenzotrifluoride | 98-16-8 | C7H6F3N | 详情 | 详情 |
| (V) | 45205 | 3-(trifluoromethyl)phenylamine; 3-(trifluoromethyl)aniline | C7H6F3N | 详情 | 详情 | |
| (VI) | 26348 | 1-bromo-3-(trifluoromethyl)benzene; 3-Bromobenzotrifluoride | 401-78-5 | C7H4BrF3 | 详情 | 详情 |
| (VI) | 45206 | 1-bromo-3-(trifluoromethyl)benzene | C7H4BrF3 | 详情 | 详情 | |
| (VII) | 12028 | Bromo[3-(trifluoromethyl)phenyl]magnesium | 402-26-6 | C7H4BrF3Mg | 详情 | 详情 |
| (VII) | 45207 | bromo[3-(trifluoromethyl)phenyl]magnesium | C7H4BrF3Mg | 详情 | 详情 | |
| (VIII) | 26349 | 1-[2-(2-naphthyl)ethyl]-4-piperidinone | C17H19NO | 详情 | 详情 | |
| (IX) | 26350 | 1-[2-(2-naphthyl)ethyl]-4-[3-(trifluoromethyl)phenyl]-4-piperidinol | C24H24F3NO | 详情 | 详情 | |
| (IX) | 45208 | 1-[2-(2-naphthyl)ethyl]-4-[3-(trifluoromethyl)phenyl]-4-piperidinol | C24H24F3NO | 详情 | 详情 | |
| (X) | 22523 | 1-nitrobenzene | 28250-14-8 | C6H5NO2 | 详情 | 详情 |
| (X) | 45209 | 1-nitrobenzene | C6H5NO2 | 详情 | 详情 | |
| (XI) | 26352 | 3-Iodonitrobenzene; 1-iodo-3-nitrobenzene | 645-00-1 | C6H4INO2 | 详情 | 详情 |
| (XI) | 45210 | 1-iodo-3-nitrobenzene | C6H4INO2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VIII)Pentadeuterated saquinavir: The nitration of hexadeuterobenzene (VII) with HNO3/H2SO4 gives pentadeuteronitrobenzene (VIII), which is hydrogenated with deuterium/Pt in D1-methanol yielding heptadeuteroaniline (IX). The cyclization of (IX) with crotonic aldehyde (II) by means of DCI/D2O and acetic anhydride as before affords hexadeuterated quinoline (X), which is brominated with Br2 as before giving the tribromo derivative (XI). The hydrolysis of (XI) with sulfuric acid as before yields the acid (XII), which is finally condensed with Ro-32-0445 (VI) as before.
| 【1】 Wiltshire, H.R.; et al.; The synthesis of labelled forms of saquinavir. J Label Compd Radiopharm 1998, 41, 12, 1103. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (II) | 22517 | (E)-2-butenal | 4170-30-3 | C4H6O | 详情 | 详情 |
| (VI) | 22521 | (2S)-N(1)-[(1S,2R)-3-[(3S,4aS,8aS)-3-[(tert-butylamino)carbonyl]octahydro-2(1H)-isoquinolinyl]-1-benzyl-2-hydroxypropyl]-2-aminobutanediamide | C28H45N5O4 | 详情 | 详情 | |
| (VII) | 13364 | Benzene | 71-43-2 | C6H6 | 详情 | 详情 |
| (VII) | 63831 | benzene | C6H6 | 详情 | 详情 | |
| (VIII) | 22523 | 1-nitrobenzene | 28250-14-8 | C6H5NO2 | 详情 | 详情 |
| (VIII) | 63832 | 1-nitrobenzene | C6H5NO2 | 详情 | 详情 | |
| (IX) | 12294 | Aniline; Phenylamine | 62-53-3 | C6H7N | 详情 | 详情 |
| (IX) | 63833 | aniline; phenylamine | C6H7N | 详情 | 详情 | |
| (X) | 13161 | Quinaldine; 2-Methylquinoline | 91-63-4 | C10H9N | 详情 | 详情 |
| (X) | 63834 | 2-methylquinoline | C10H9N | 详情 | 详情 | |
| (XI) | 22526 | 2-(tribromomethyl)quinoline | 613-53-6 | C10H6Br3N | 详情 | 详情 |
| (XI) | 63835 | 2-(tribromomethyl)quinoline | C10H6Br3N | 详情 | 详情 | |
| (XII) | 14532 | 2-Quinolinecarboxylic acid; Quinaldic Acid | 93-10-7 | C10H7NO2 | 详情 | 详情 |
| (XII) | 63836 | 2-quinolinecarboxylic acid | C10H7NO2 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(XXII)5)[15N,13C,2H]-Saquinavir: The nitration of [13C6]-benzene (XXI) with [15N]-nitric acid gives the corresponding nitrobenzene (XXII), which is reduced with Sn/HCl to the aniline (XXIII). The cyclization of (XXIII) with crotonic aldehyde (II) by means of ClD/D2O and acetic ahydride yields the tetradeuterated quinoline (XXIV), which is brominated as before givig the tribromo derivative (XXV). The hydrolysis of (XXV) with sulfuric acid as usual affords the [15N,13C6,2H3]-labeled quinoline-2-carboxylic acid (XXVI), which is finally condensed with Ro-32-0445 (VI) by means of HOBT and CDI as indicated.
| 【1】 Wiltshire, H.R.; et al.; The synthesis of labelled forms of saquinavir. J Label Compd Radiopharm 1998, 41, 12, 1103. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (II) | 22517 | (E)-2-butenal | 4170-30-3 | C4H6O | 详情 | 详情 |
| (VI) | 22521 | (2S)-N(1)-[(1S,2R)-3-[(3S,4aS,8aS)-3-[(tert-butylamino)carbonyl]octahydro-2(1H)-isoquinolinyl]-1-benzyl-2-hydroxypropyl]-2-aminobutanediamide | C28H45N5O4 | 详情 | 详情 | |
| (XI) | 22526 | 2-(tribromomethyl)quinoline | 613-53-6 | C10H6Br3N | 详情 | 详情 |
| (XI) | 45225 | 2-(tribromomethyl)quinoline | C10H6Br3N | 详情 | 详情 | |
| (XII) | 14532 | 2-Quinolinecarboxylic acid; Quinaldic Acid | 93-10-7 | C10H7NO2 | 详情 | 详情 |
| (XII) | 45226 | 2-quinolinecarboxylic acid | C10H7NO2 | 详情 | 详情 | |
| (XXI) | 13364 | Benzene | 71-43-2 | C6H6 | 详情 | 详情 |
| (XXI) | 22536 | benzene | C6H6 | 详情 | 详情 | |
| (XXII) | 22523 | 1-nitrobenzene | 28250-14-8 | C6H5NO2 | 详情 | 详情 |
| (XXII) | 22537 | 1-nitrobenzene | C6H5NO2 | 详情 | 详情 | |
| (XXIII) | 12294 | Aniline; Phenylamine | 62-53-3 | C6H7N | 详情 | 详情 |
| (XXIII) | 22538 | phenylamine; aniline | C6H7N | 详情 | 详情 | |
| (XXIV) | 13161 | Quinaldine; 2-Methylquinoline | 91-63-4 | C10H9N | 详情 | 详情 |
| (XXIV) | 45224 | 2-methylquinoline | C10H9N | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：By condensation of biphenyl (I) and succinic anhydride (II) in nitrobenzene, using AlCl3, as catalyst.
| 【1】 Castañer, J.; Fenbufen. Drugs Fut 1976, 1, 1, 21. |
| 【2】 Tomeufeik, A.; et al. (American Cyanamid Co.); Compositions containing substituted benzoylpropionic acids and method of use to treat inflammation and pain. DE 2147111; FR 2107848; GB 1320076; US 3784701 . |