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【结 构 式】 
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【分子编号】22526 【品名】2-(tribromomethyl)quinoline 【CA登记号】613-53-6 |
【 分 子 式 】C10H6Br3N 【 分 子 量 】379.87638 【元素组成】C 31.62% H 1.59% Br 63.1% N 3.69% |
合成路线1
该中间体在本合成路线中的序号：(IV)[14C]-Saquinavir: The cyclization of [ring-14C]-aniline (I) with crotonic aldehyde (II) by means of HCl and acetic anhydride gives labeled 2-methylquinoline (III), which is brominated with Br2 in acetic acid yielding the tribromo derivative (IV). The hydrolysis of (IV) with hot sulfuric acid afforded labeled quinoline-2-carboxylic acid (V), which is finally condensed with Ro-32-0445 (VI) by means of hydroxybenzotriazole (HOBT) and dicyclohexylcarbodiimide (DCC) in THF.
| 【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 |
|---|---|---|---|---|---|---|
| (I) | 12294 | Aniline; Phenylamine | 62-53-3 | C6H7N | 详情 | 详情 |
| (I) | 22516 | aniline; phenylamine | C6H7N | 详情 | 详情 | |
| (II) | 22517 | (E)-2-butenal | 4170-30-3 | C4H6O | 详情 | 详情 |
| (III) | 13161 | Quinaldine; 2-Methylquinoline | 91-63-4 | C10H9N | 详情 | 详情 |
| (III) | 22518 | 2-methylquinoline | C10H9N | 详情 | 详情 | |
| (IV) | 22519 | 2-(tribromomethyl)quinoline | C10H6Br3N | 详情 | 详情 | |
| (IV) | 22526 | 2-(tribromomethyl)quinoline | 613-53-6 | C10H6Br3N | 详情 | 详情 |
| (V) | 14532 | 2-Quinolinecarboxylic acid; Quinaldic Acid | 93-10-7 | C10H7NO2 | 详情 | 详情 |
| (V) | 22520 | 2-quinolinecarboxylic acid | C10H7NO2 | 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 |
合成路线2
该中间体在本合成路线中的序号：(XI)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：(XIV)Tetradeuterated saquinavir: The cyclization of heptadeuteroaniline (IX) with crotonic aldehyde (II) by means of HCl and acetic anhydride as before gives the tetradeuteroquinoline (XIII), which is brominated as described yielding the tribromo derivative (XIV). The hydrolysis of (XIV) with sulfuric acid affords tetradeuterated acid (XV), which is finally condensed with Ro-32-0445 (VI) 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 | |
| (IX) | 12294 | Aniline; Phenylamine | 62-53-3 | C6H7N | 详情 | 详情 |
| (IX) | 63833 | aniline; phenylamine | C6H7N | 详情 | 详情 | |
| (XIII) | 13161 | Quinaldine; 2-Methylquinoline | 91-63-4 | C10H9N | 详情 | 详情 |
| (XIII) | 63834 | 2-methylquinoline | C10H9N | 详情 | 详情 | |
| (XIV) | 22526 | 2-(tribromomethyl)quinoline | 613-53-6 | C10H6Br3N | 详情 | 详情 |
| (XV) | 14532 | 2-Quinolinecarboxylic acid; Quinaldic Acid | 93-10-7 | C10H7NO2 | 详情 | 详情 |
| (XV) | 63836 | 2-quinolinecarboxylic acid | C10H7NO2 | 详情 | 详情 | |
| (XVI) | 63835 | 2-(tribromomethyl)quinoline | C10H6Br3N | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(XI)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 |