2-(1-ethylpropyl)-4-[4-[4-(4-hydroxyphenyl)piperazino]phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one -Drug Synthesis Database

【结构式】

【分子编号】16310

【品名】2-(1-ethylpropyl)-4-[4-[4-(4-hydroxyphenyl)piperazino]phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one

【CA登记号】

【分子式】C₂₃H₂₉N₅O₂

【分子量】407.51576

【元素组成】C 67.79% H 7.17% N 17.19% O 7.85%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(I)

SCH 51048 is synthesized by condensation of 4-[4-(4-hydroxyphenyl)piperazin-1-yl]phenyl]-2-(1-ethylpropyl)-3,4-dihydro-2H-1,2,4-triazol-3-one (I) with (-)-(5R-cis)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl) tetrahydrofuran-3-methanol tosylate (II) by means of NaH in DMSO.

参考文献中间体

合成目标

【1】 Van Cutsem, J.; Backx, L.J.J.; Heeres, J.; J. Antimycotic azoles. 7. Synthesis and antifungal properties of a series of novel triazol-3-ones. J Med Chem 1984, 27, 7, 894-900.
【2】 Castañer, J.; Fromtling, R.A.; SCH 51048. Drugs Fut 1995, 20, 3, 241.
【3】 Saksena, A.K.; Girijavallabhan, V.M.; Ganguly, A.K.; Lovey, R.G. (Schering Corp.); Tri-substd. tetrahydrofuran antifungals. EP 0610377; JP 1995500605; WO 9309114 .

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)	16310	2-(1-ethylpropyl)-4-[4-[4-(4-hydroxyphenyl)piperazino]phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one		C₂₃H₂₉N₅O₂	详情	详情
(II)	16311	[(3S,5R)-5-(2,4-difluorophenyl)-5-(1H-1,2,4-triazol-1-ylmethyl)tetrahydro-3-furanyl]methyl 4-methylbenzenesulfonate		C₂₁H₂₁F₂N₃O₄S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

The intermediate (I) can be obtained as follows:1) The condensation of 1-(4-methoxyphenyl)piperazine (III) with chloronitrobenzene (IV) by means of K2CO3 in DMSO gives 1-(4-methoxyphenyl)-4-(4-nitrophenyl)piperazine (V), which is reduced with H2 over Pt/C to the corresponding amine (VI). The reaction of (VI) with phenyl chloroformate and pyridine in CHCl3 affords the corresponding carbamate (VII), which is treated with hydrazine in dioxane/water yielding the semicarbazide (VIII). The cyclization of (VIII) with formamidine and sodium acetate in butanol gives 4-[4-[4-(4-methoxyphenyl)piperazin-1-yl]phenyl]-3,4-dihydro-2H-1,2,4-triazol-3-one (IX) (2), which is alkylated with 1-ethylpropyl tosylate (X) by means of KOH in DMSO yielding the corresponding 2-alkyl compound (XI). Finally, this compound is demethylated to (I) by refluxing in 48% HBr.

参考文献中间体

合成目标

【1】 Van Cutsem, J.; Backx, L.J.J.; Heeres, J.; J. Antimycotic azoles. 7. Synthesis and antifungal properties of a series of novel triazol-3-ones. J Med Chem 1984, 27, 7, 894-900.
【2】 Castañer, J.; Fromtling, R.A.; SCH 51048. Drugs Fut 1995, 20, 3, 241.
【3】 Saksena, A.K.; Girijavallabhan, V.M.; Ganguly, A.K.; Lovey, R.G. (Schering Corp.); Tri-substd. tetrahydrofuran antifungals. EP 0610377; JP 1995500605; WO 9309114 .

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)	16310	2-(1-ethylpropyl)-4-[4-[4-(4-hydroxyphenyl)piperazino]phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one		C₂₃H₂₉N₅O₂	详情	详情
(III)	16312	1-(4-Methoxyphenyl)piperazine; Methyl 4-piperazinophenyl ether	38212-30-5	C₁₁H₁₆N₂O	详情	详情
(IV)	13909	1-Chloro-4-nitrobenzene; p-Nitrochlorobenzene	100-00-5	C₆H₄ClNO₂	详情	详情
(V)	16314	methyl 4-[4-(4-nitrophenyl)piperazino]phenyl ether; 1-(4-methoxyphenyl)-4-(4-nitrophenyl)piperazine		C₁₇H₁₉N₃O₃	详情	详情
(VI)	16315	4-[4-(4-methoxyphenyl)piperazino]phenylamine; 4-[4-(4-methoxyphenyl)piperazino]aniline; 1-(4-Aminophenyl)-4-(4-methoxyphenyl)piperazine	74852-62-3	C₁₇H₂₁N₃O	详情	详情
(VII)	16316	phenyl N-[4-[4-(4-methoxyphenyl)piperazino]phenyl]carbamate		C₂₄H₂₅N₃O₃	详情	详情
(VIII)	16317	N-[4-[4-(4-methoxyphenyl)piperazino]phenyl]-1-hydrazinecarboxamide		C₁₈H₂₃N₅O₂	详情	详情
(IX)	16318	4-[4-[4-(4-methoxyphenyl)piperazino]phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one		C₁₉H₂₁N₅O₂	详情	详情
(X)	16319	1-ethylpropyl 4-methylbenzenesulfonate		C₁₂H₁₈O₃S	详情	详情
(XI)	16320	2-(1-ethylpropyl)-4-[4-[4-(4-methoxyphenyl)piperazino]phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one		C₂₄H₃₁N₅O₂	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

The synthesis of [3H]-SCH-51048 has been described:The tritiation of phenol (I) with tritiated heptafluorobutyric acid at 115 C gives the polytritiated intermediate (II), which is then condensed with the chiral tosylate (III) by means of NaOH in DMSO affording labeled SCH-51048.

参考文献中间体

合成目标

【1】 Magatti, C.V.; et al.; Synthesis of H-3-SCH 51048 and C-14-SCH 56592. J Label Compd Radiopharm 1998, 41, 8, 731.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	16310	2-(1-ethylpropyl)-4-[4-[4-(4-hydroxyphenyl)piperazino]phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one	C₂₃H₂₉N₅O₂	详情	详情
(II)	22485	2-(1-ethylpropyl)-4-[4-[4-(4-hydroxyphenyl)-1-piperazinyl]phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one	C₂₃H₂₉N₅O₂	详情	详情
(II)	45295	2-(1-ethylpropyl)-4-[4-[4-(4-hydroxyphenyl)-1-piperazinyl]phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one	C₂₃H₂₉N₅O₂	详情	详情
(III)	16311	[(3S,5R)-5-(2,4-difluorophenyl)-5-(1H-1,2,4-triazol-1-ylmethyl)tetrahydro-3-furanyl]methyl 4-methylbenzenesulfonate	C₂₁H₂₁F₂N₃O₄S	详情	详情

Extended Information