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【结 构 式】 
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【分子编号】30174 【品名】(3aR,7aR)-1,2,3-trimethyloctahydro-1H-1,3,2lambda(5)-benzodiazaphosphol-2-one 【CA登记号】 |
【 分 子 式 】C9H19N2OP 【 分 子 量 】202.236502 【元素组成】C 53.45% H 9.47% N 13.85% O 7.91% P 15.32% |
合成路线1
该中间体在本合成路线中的序号：(X)The cyclization of (R,R)-N,N'-dimethylcyclohexane-1,2-diamine (I) with methylphosphonic acid dichloride by means of triethylamine in benzene gives the 1,2,3-trimethyloctahydro-1,3,2-benzodiazaphosphole (X), which is condensed with 3-(3-phenoxyphenyl)propyl iodide (XI) by means of BuLi in THF yielding the 2-[4-(3-phenoxyphenyl)butyl] derivative (XII). The condensation of (XII) with tetramethylthiuram disulfide (XIII) by means of BuLi in THF affords, after chromatographic resolution of the resulting diastereomeric mixture, the previously reported dithiocarbamic ester (VII), which is hydrolyzed to the phosphonic acid (VIII), which is oxidized with HCO2H and H2O2 in acetic acid affording the target sulfonic acid (IX).
| 【1】 Magnin, D.R.; Biller, S.A.; Dickson, J.K. Jr.; Lawrence, M.R.; Sulsky, R.B. (Bristol-Myers Squibb Co.); Alpha-phosphorous substd. sulfonate derivs. as squalene synthetase inhibitors. EP 0595635; JP 1994199879; US 5712396 . |
| 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) | 30165 | trans-(1R,2R)-N,N'-Bismethyl-1,2-cyclohexanediamine; (1R,2R)-N(1),N(2)-dimethyl-1,2-cyclohexanediamine; N-methyl-N-[(1R,2R)-2-(methylamino)cyclohexyl]amine | 67579-81-1 | C8H18N2 | 详情 | 详情 |
| (VII) | 30171 | (1S)-1-[(3aR,7aR)-1,3-dimethyl-2-oxooctahydro-1H-1,3,2lambda(5)-benzodiazaphosphol-2-yl]-4-(3-phenoxyphenyl)butyl dimethylcarbamodithioate | C27H38N3O2PS2 | 详情 | 详情 | |
| (VIII) | 30172 | (1S)-1-[[(dimethylamino)carbothioyl]sulfanyl]-4-(3-phenoxyphenyl)butylphosphonic acid | C19H24NO4PS2 | 详情 | 详情 | |
| (X) | 30174 | (3aR,7aR)-1,2,3-trimethyloctahydro-1H-1,3,2lambda(5)-benzodiazaphosphol-2-one | C9H19N2OP | 详情 | 详情 | |
| (XI) | 30175 | 3-(3-iodopropyl)phenyl phenyl ether; 1-(3-iodopropyl)-3-phenoxybenzene | C15H15IO | 详情 | 详情 | |
| (XII) | 30176 | (3aR,7aR)-1,3-dimethyl-2-[4-(3-phenoxyphenyl)butyl]octahydro-1H-1,3,2lambda(5)-benzodiazaphosphol-2-one | C24H33N2O2P | 详情 | 详情 | |
| (XIII) | 30177 | [([[(dimethylamino)carbothioyl]disulfanyl]carbothioyl)(methyl)amino]methane | 137-26-8 | C6H12N2S4 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(X)The cyclization of (R,R)-N,N'-dimethylcyclohexane-1,2-diamine (I) with methylphosphonic acid dichloride by means of triethylamine in benzene gives the 1,2,3-trimethyloctahydro-1,3,2-benzodiazaphosphole (X), which is condensed with 3-(3-phenoxyphenyl)propyl iodide (XI) by means of BuLi in THF yielding the 2-[4-(3-phenoxyphenyl)butyl] derivative (XII). The condensation of (XII) with tetramethylthiuram disulfide (XIII) by means of BuLi in THF affords, after chromatographic resolution of the resulting diastereomeric mixture, the previously reported dithiocarbamic ester (VII), which is hydrolyzed to the phosphonic acid (VIII), which is oxidized with HCOOH and H2O2 in acetic acid affording the intermediate sulfonic acid (IX).
| 【1】 Magnin, D.R.; Biller, S.A.; Dickson, J.K. Jr.; Lawrence, M.R.; Sulsky, R.B. (Bristol-Myers Squibb Co.); Alpha-phosphorous substd. sulfonate derivs. as squalene synthetase inhibitors. EP 0595635; JP 1994199879; US 5712396 . |
| 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) | 30165 | trans-(1R,2R)-N,N'-Bismethyl-1,2-cyclohexanediamine; (1R,2R)-N(1),N(2)-dimethyl-1,2-cyclohexanediamine; N-methyl-N-[(1R,2R)-2-(methylamino)cyclohexyl]amine | 67579-81-1 | C8H18N2 | 详情 | 详情 |
| (VII) | 30171 | (1S)-1-[(3aR,7aR)-1,3-dimethyl-2-oxooctahydro-1H-1,3,2lambda(5)-benzodiazaphosphol-2-yl]-4-(3-phenoxyphenyl)butyl dimethylcarbamodithioate | C27H38N3O2PS2 | 详情 | 详情 | |
| (VIII) | 30172 | (1S)-1-[[(dimethylamino)carbothioyl]sulfanyl]-4-(3-phenoxyphenyl)butylphosphonic acid | C19H24NO4PS2 | 详情 | 详情 | |
| (IX) | 30173 | (1S)-4-(3-phenoxyphenyl)-1-phosphono-1-butanesulfonic acid | C16H19O7PS | 详情 | 详情 | |
| (X) | 30174 | (3aR,7aR)-1,2,3-trimethyloctahydro-1H-1,3,2lambda(5)-benzodiazaphosphol-2-one | C9H19N2OP | 详情 | 详情 | |
| (XI) | 30175 | 3-(3-iodopropyl)phenyl phenyl ether; 1-(3-iodopropyl)-3-phenoxybenzene | C15H15IO | 详情 | 详情 | |
| (XII) | 30176 | (3aR,7aR)-1,3-dimethyl-2-[4-(3-phenoxyphenyl)butyl]octahydro-1H-1,3,2lambda(5)-benzodiazaphosphol-2-one | C24H33N2O2P | 详情 | 详情 | |
| (XIII) | 30177 | [([[(dimethylamino)carbothioyl]disulfanyl]carbothioyl)(methyl)amino]methane | 137-26-8 | C6H12N2S4 | 详情 | 详情 |