Diisopropyl [(4-chlorophenyl)sulfanyl](diisopropoxyphosphoryl)methylphosphonate -Drug Synthesis Database

【结构式】

【分子编号】10200

【品名】Diisopropyl [(4-chlorophenyl)sulfanyl](diisopropoxyphosphoryl)methylphosphonate

【CA登记号】

【分子式】C₁₉H₃₃ClO₆P₂S

【分子量】486.933644

【元素组成】C 46.87% H 6.83% Cl 7.28% O 19.71% P 12.72% S 6.59%

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：(VII)

A synthesis for [benzene-U-14C]-tiludronate has been described: The chlorination of [U-14C]-acetanilide (I) with tetrabutylammonium iodotetrachloride gives the corresponding 4-chloro derivative (II) (along with some of the 2-chloro isomer). The hydrolysis of (II) with concentrated HCl at 60 C yields the chloroaniline (III), which is converted to the corresponding diazonium salt (IV) with NaNO2 and HCl. The reaction of (IV) with ferric thiocyanate affords the labeled 4-chlorophenylthiocyanate (V), which is condensed with the lithium salt of methylenebis(phosphonic acid)tetraisopropyl ester (VI) in THF to yield 4-chlorophenylsulfanylmethylenebis(phosphonic acid)tetraisopropyl ester (VII). Finally, this compound is hydrolyzed with concentrated HCl or aqueous NaOH.

参考文献中间体

合成目标

【1】 Ellames, G.J.; Burgos, A.; Synthesis of disodium [benzene-U-C-14]-(4-chlorophenylthio)methylene diphosphonate, [benzene-U-C-14]-tiludronate. J Label Compd Radiopharm 1995, 36, 11, 1071.

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)	10194	N-Phenylacetamide; Acetanilide	103-84-4	C₈H₉NO	详情	详情
(I)	44610			C₈H₉NO	详情	详情
(II)	10195	N-(4-Chlorophenyl)acetamide	539-03-7	C₈H₈ClNO	详情	详情
(II)	44611			C₈H₈ClNO	详情	详情
(III)	10196	4-Chlorobenzenaminium chloride		C₆H₇Cl₂N	详情	详情
(III)	44612			C₆H₇Cl₂N	详情	详情
(IV)	10197	4-Chlorobenzenediazonium chloride		C₆H₄Cl₂N₂	详情	详情
(IV)	44613			C₆H₇Cl₂N	详情	详情
(V)	10198	4-Chlorophenyl thiocyanate	3226-37-7	C₇H₄ClNS	详情	详情
(V)	44614			C₇H₄ClNS	详情	详情
(VI)	10199	[Bis(diisopropoxyphosphoryl)methyl]lithium		C₁₃H₂₉LiO₆P₂	详情	详情
(VII)	10200	Diisopropyl [(4-chlorophenyl)sulfanyl](diisopropoxyphosphoryl)methylphosphonate		C₁₉H₃₃ClO₆P₂S	详情	详情
(VII)	44615			C₁₉H₃₃ClO₆P₂S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

The reaction of di(4-chlorophenyl)disulfide (I) with tetraisopropyl methylenediphosphonate (II) by means of NaH in hot DMF gives tetraisopropyl (4-chlorophenyl)thiomethylenediphosphonate (III), which is finally hydrolyzed with refluxing aqueous 6N HCl.

参考文献中间体

合成目标

【1】 Shirasaki, M. (Sanofi-Synthelabo); Polarizing elements. DE 3378140; EP 0100718 .
【2】 Serradell, M.N.; Castaner, J.; SR-41319. Drugs Fut 1985, 10, 6, 482.

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)	29707	bis(4-chlorophenyl) disulfide; 1-chloro-4-[(4-chlorophenyl)disulfanyl]benzene	1142-19-4	C₁₂H₈Cl₂S₂	详情	详情
(II)	27980	Diisopropyl (diisopropoxyphosphoryl)methylphosphonate; Tetraisopropyl methylenediphosphonate	1660-95-3	C₁₃H₃₀O₆P₂	详情	详情
(III)	10200	Diisopropyl [(4-chlorophenyl)sulfanyl](diisopropoxyphosphoryl)methylphosphonate		C₁₉H₃₃ClO₆P₂S	详情	详情

Extended Information