(3aR,7aR)-2-chloro-1,3-dimethyloctahydro-1H-1,3,2lambda(5)-benzodiazaphosphol-2-one -Drug Synthesis Database

【结构式】

【分子编号】30178

【品名】(3aR,7aR)-2-chloro-1,3-dimethyloctahydro-1H-1,3,2lambda(5)-benzodiazaphosphol-2-one

【CA登记号】

【分子式】C₈H₁₆ClN₂OP

【分子量】222.654382

【元素组成】C 43.16% H 7.24% Cl 15.92% N 12.58% O 7.19% P 13.91%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(XIV)

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.

参考文献中间体

合成目标

【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：(XIV)

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.

参考文献中间体

合成目标

【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

Extended Information