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【结 构 式】 
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【分子编号】30179 【品名】ethyl [(3aR,7aR)-1,3-dimethyl-2-oxooctahydro-1H-1,3,2lambda(5)-benzodiazaphosphol-2-yl]methanesulfonate 【CA登记号】 |
【 分 子 式 】C11H23N2O4PS 【 分 子 量 】310.354462 【元素组成】C 42.57% H 7.47% N 9.03% O 20.62% P 9.98% S 10.33% |
合成路线1
该中间体在本合成路线中的序号：(XV)The cyclization of (R,R)-N,N'-dimethylcyclohexane-1,2-diamine (I) with POCl3 by means of triethylamine in THF gives the 2-chlorooctahydro-1,3,2-benzodiazaphophole (XIV), which is condensed with ethyl methanesulfonate by means of BuLi in THF yielding the substituted methanesulfonate (XV). The hydrolysis of (XV) with tetrabutylammonium iodide in THF affords the corresponding tetrabutylammonium sulfonate (XVI), which is then condensed with 3-(3-phenoxyphenyl) propyl iodide (XI) by means of BuLi in THF giving the precursor sulfonic acid (XVII). Finally, this compound is hydrolyzed to the target compound with HCl.
| 【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 |
| (XI) | 30175 | 3-(3-iodopropyl)phenyl phenyl ether; 1-(3-iodopropyl)-3-phenoxybenzene | C15H15IO | 详情 | 详情 | |
| (XIV) | 30178 | (3aR,7aR)-2-chloro-1,3-dimethyloctahydro-1H-1,3,2lambda(5)-benzodiazaphosphol-2-one | C8H16ClN2OP | 详情 | 详情 | |
| (XV) | 30179 | ethyl [(3aR,7aR)-1,3-dimethyl-2-oxooctahydro-1H-1,3,2lambda(5)-benzodiazaphosphol-2-yl]methanesulfonate | C11H23N2O4PS | 详情 | 详情 | |
| (XVI) | 30180 | N,N,N-tributyl-1-butanaminium [(3aR,7aR)-1,3-dimethyl-2-oxooctahydro-1H-1,3,2lambda(5)-benzodiazaphosphol-2-yl]methanesulfonate | C25H54N3O4PS | 详情 | 详情 | |
| (XVII) | 30181 | (1S)-1-[(3aR,7aR)-1,3-dimethyl-2-oxooctahydro-1H-1,3,2lambda(5)-benzodiazaphosphol-2-yl]-4-(3-phenoxyphenyl)-1-butanesulfonic acid | C24H33N2O5PS | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XV)The cyclization of (R,R)-N,N'-dimethylcyclohexane-1,2-diamine (I) with POCl3 by means of triethylamine in THF gives the 2-chlorooctahydro-1,3,2-benzodiazaphophole (XIV), which is condensed with ethyl methanesulfonate by means of BuLi in THF yielding the substituted methanesulfonate (XV). The hydrolysis of (XV) with tetrabutylammonium iodide in THF affords the correponding tetrabutylammonium sulfonate (XVI), which is then condensed with 3-(3-phenoxyphenyl)propyl iodide (XI) by means of BuLi in THF giving the precursor sulfonic acid (XVII). Finally, this compound is hydrolyzed to the intermediate sulfonic acid compound (IX) with HCl.
| 【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 |
| (IX) | 30173 | (1S)-4-(3-phenoxyphenyl)-1-phosphono-1-butanesulfonic acid | C16H19O7PS | 详情 | 详情 | |
| (XI) | 30175 | 3-(3-iodopropyl)phenyl phenyl ether; 1-(3-iodopropyl)-3-phenoxybenzene | C15H15IO | 详情 | 详情 | |
| (XIV) | 30178 | (3aR,7aR)-2-chloro-1,3-dimethyloctahydro-1H-1,3,2lambda(5)-benzodiazaphosphol-2-one | C8H16ClN2OP | 详情 | 详情 | |
| (XV) | 30179 | ethyl [(3aR,7aR)-1,3-dimethyl-2-oxooctahydro-1H-1,3,2lambda(5)-benzodiazaphosphol-2-yl]methanesulfonate | C11H23N2O4PS | 详情 | 详情 | |
| (XVI) | 30180 | N,N,N-tributyl-1-butanaminium [(3aR,7aR)-1,3-dimethyl-2-oxooctahydro-1H-1,3,2lambda(5)-benzodiazaphosphol-2-yl]methanesulfonate | C25H54N3O4PS | 详情 | 详情 | |
| (XVII) | 30181 | (1S)-1-[(3aR,7aR)-1,3-dimethyl-2-oxooctahydro-1H-1,3,2lambda(5)-benzodiazaphosphol-2-yl]-4-(3-phenoxyphenyl)-1-butanesulfonic acid | C24H33N2O5PS | 详情 | 详情 |