1-(3-chlorophenyl)piperazine -Drug Synthesis Database

【结构式】

【分子编号】22114

【品名】1-(3-chlorophenyl)piperazine

【CA登记号】6640-24-0

【分子式】C₁₀H₁₃ClN₂

【分子量】196.6794

【元素组成】C 61.07% H 6.66% Cl 18.03% N 14.24%

与该中间体有关的原料药合成路线共 6 条

合成路线1 合成路线2 合成路线3 合成路线4 合成路线5 合成路线6

合成路线1

该中间体在本合成路线中的序号：(I)

1) The condensation of a phenylpiperazine (I) with chloroethanol (II) gives compound (III) which, upon reaction with the acid chloride (IV), yields lobuprofen.

参考文献中间体

合成目标

【1】 Alamo Gonzalez, C.; Carretero Colon, J.M.; Martin Jimenez, J.L. (Juste, SA Quimico-Farmaceutica); Novel phenylpiperazine derivs., process for prepar. EP 0141884 .
【2】 Carretero, J.M.; Alamo, C.; Martin, J.L.; Lobuprofen hydrochloride. Drugs Fut 1988, 13, 4, 314.

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)	22114	1-(3-chlorophenyl)piperazine	6640-24-0	C₁₀H₁₃ClN₂	详情	详情
(II)	10384	2-Chloro-1-ethanol; Ethylene chlorohydrin	107-07-3	C₂H₅ClO	详情	详情
(III)	22116	2-[4-(3-chlorophenyl)-1-piperazinyl]-1-ethanol		C₁₂H₁₇ClN₂O	详情	详情
(IV)	22117	2-(4-isobutylphenyl)propanoyl chloride		C₁₃H₁₇ClO	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

2) The acid chloride (IV) is reacted with chloroethanol to give compound (V), which, upon condensation with a piperazine (I), yields lobuprofen.

参考文献中间体

合成目标

【1】 Alamo Gonzalez, C.; Carretero Colon, J.M.; Martin Jimenez, J.L. (Juste, SA Quimico-Farmaceutica); Novel phenylpiperazine derivs., process for prepar. EP 0141884 .
【2】 Prous, J.; Castaner, J.; ONO-RS-411. Drugs Fut 1988, 13, 4, 317.

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)	22114	1-(3-chlorophenyl)piperazine	6640-24-0	C₁₀H₁₃ClN₂	详情	详情
(II)	10384	2-Chloro-1-ethanol; Ethylene chlorohydrin	107-07-3	C₂H₅ClO	详情	详情
(IV)	22117	2-(4-isobutylphenyl)propanoyl chloride		C₁₃H₁₇ClO	详情	详情
(V)	22118	2-chloroethyl 2-(4-isobutylphenyl)propanoate		C₁₅H₂₁ClO₂	详情	详情

合成路线3

该中间体在本合成路线中的序号：(IV)

The condensation of 5-methoxy-1,2,3,4-tetrahydroquinolin-2-one (I) with 1,3-dichloropropane (II) by means of NaH in DMF gives 1-(3-chloropropyl)-5-methoxy-1,2,3,4-tetrahydroquinolin-2-one (II), which is finally condensed with 1-(3-chlorophenyl)piperazine (IV) by means of NaI and K2CO3 in acetonitrile.

参考文献中间体

合成目标

【1】 Oshiro, Y.; et al.; 3,4-Dihydro-2(1H)-quinolinone as a novel antidepressant drug: Synthesis and pharmacology of 1-[3-[4-(3-chlorophenyl)-1-piperazinyl]propyl]-3,4-dihydro-5-methoxy-2(1H)-quinolinone and its derivatives. J Med Chem 2000, 43, 2, 177.

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)	38679	5-methoxy-3,4-dihydro-2(1H)-quinolinone		C₁₀H₁₁NO₂	详情	详情
(II)	38680	1,3-dichloropropane	142-28-9	C₃H₆Cl₂	详情	详情
(III)	38681	1-(3-chloropropyl)-5-methoxy-3,4-dihydro-2(1H)-quinolinone		C₁₃H₁₆ClNO₂	详情	详情
(IV)	22114	1-(3-chlorophenyl)piperazine	6640-24-0	C₁₀H₁₃ClN₂	详情	详情

合成路线4

该中间体在本合成路线中的序号：(IV)

Pyrimidinyl pyrazole (III) was prepared by condensation of diketone (I) with 2-hydrazinopyrimidine (II). Subsequent Mannich reaction with N-(3-chlorophenyl)piperazine (IV) and paraformaldehyde furnished piperazinyl propanone (V). This was reduced to alcohol (VI) with NaBH4. Alcohol dehydration employing p-toluenesulfonic acid yielded the title compound, that was finally isolated as the hydrochloride salt. The intermediate N-(3-chlorophenyl)piperazine (IV) has been obtained by cyclization of bis(2-chloroethyl)amine (VII) with 3-chloroaniline (VIII) by means of Na2CO3 in refluxing butanol.

参考文献中间体

合成目标

【1】 DE 2038503; US 3723433 .
【2】 Ejima, A.; Sugimori, M.; Mitsui, I. (Daiichi Pharmaceutical Co., Ltd.); Pyrimidinylpyrazole deriv.. EP 0784055; JP 1997048776; US 5852019; WO 9610024 .
【3】 Ishii, M.; Ejima, A.; Hirotani, K.; Iwahana, M.; Sugimori, M.; Mitsui, I.; Naito, H.; Nakamura, Y.; Synthesis and antitumor activity of novel pyrimidinyl pyrazole derivatives. Chem Pharm Bull 1999, 47, 12, 1679.

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)	41449	3-(ethoxymethylene)-2,4-pentanedione		C₈H₁₂O₃	详情	详情
(II)	41450	2-hydrazinopyrimidine		C₄H₆N₄	详情	详情
(III)	41451	1-[5-methyl-1-(2-pyrimidinyl)-1H-pyrazol-4-yl]-1-ethanone		C₁₀H₁₀N₄O	详情	详情
(IV)	22114	1-(3-chlorophenyl)piperazine	6640-24-0	C₁₀H₁₃ClN₂	详情	详情
(V)	41452	3-[4-(3-chlorophenyl)-1-piperazinyl]-1-[5-methyl-1-(2-pyrimidinyl)-1H-pyrazol-4-yl]-1-propanone		C₂₁H₂₃ClN₆O	详情	详情
(VI)	41453	3-[4-(3-chlorophenyl)-1-piperazinyl]-1-[5-methyl-1-(2-pyrimidinyl)-1H-pyrazol-4-yl]-1-propanol		C₂₁H₂₅ClN₆O	详情	详情
(VII)	21583	2-chloro-N-(2-chloroethyl)-1-ethanamine; Bis(2-chloroethyl)amine; 1,1'-iminobis(2-chloroethane); N,N-bis(2-chloroethyl)amine	821-48-7	C₄H₉Cl₂N	详情	详情
(VIII)	25239	3-chloroaniline; 3-chlorophenylamine	108-42-9	C₆H₆ClN	详情	详情

合成路线5

该中间体在本合成路线中的序号：(V)

Oxazinone (II) was prepared by cyclization of the unsaturated keto acid (I) with hydroxylamine. Subsequent radical bromination of (II) with N-bromosuccinimide (NBS) provided the alpha-bromobenzyl derivative (III). Alkylation of 3-chlorophenyl piperazine (IV) with N-(2-bromoethyl)phthalimide (V) gave adduct (VI). Further hydrazinolysis of the phthaloyl group of (VI) yielded the primary amine (VII). Finally, condensation between bromide (III) and amine (VII) in refluxing THF furnished the title 5-amino oxazinone derivative.

参考文献中间体

合成目标

【1】 Rubat, C.; Bebot, M.; Fialip, J.; Coudert, P.; Courteix, C.; Couquelet, J.; Synthesis and analgesic effects of 5-[4-(arylpiperazin-1-yl)alkylamino]-4-benzyl-3-methyl-1,2-oxazin-6-ones. Arzneim-Forsch Drug Res 2000, 50, 4, 353.

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)	46968	(E)-3-benzyl-4-oxo-2-pentenoic acid		C₁₂H₁₂O₃	详情	详情
(II)	46969	4-benzyl-3-methyl-6H-1,2-oxazin-6-one		C₁₂H₁₁NO₂	详情	详情
(III)	46970	4-[bromo(phenyl)methyl]-3-methyl-6H-1,2-oxazin-6-one		C₁₂H₁₀BrNO₂	详情	详情
(IV)	37025	2-(2-bromoethyl)-1H-isoindole-1,3(2H)-dione	574-98-1	C₁₀H₈BrNO₂	详情	详情
(V)	22114	1-(3-chlorophenyl)piperazine	6640-24-0	C₁₀H₁₃ClN₂	详情	详情
(VI)	46971	2-[2-[4-(3-chlorophenyl)-1-piperazinyl]ethyl]-1H-isoindole-1,3(2H)-dione		C₂₀H₂₀ClN₃O₂	详情	详情
(VII)	46972	2-[4-(3-chlorophenyl)-1-piperazinyl]-1-ethanamine; 2-[4-(3-chlorophenyl)-1-piperazinyl]ethylamine		C₁₂H₁₈ClN₃	详情	详情

合成路线6

该中间体在本合成路线中的序号：(I)

N-(3-Chlorophenyl)piperazine (I) is alkylated with 1-bromo-2-chloroethane in the presence of NaOH in DMSO to afford the (2-chloroethyl)piperazine (II). Subsequent condensation of alkyl chloride (II) with 4,5,6,7-tetrahydro-1H-indol-4-one (III) gives rise to the title compound

参考文献中间体

合成目标

【1】 Foreman, M.M.; Helton, D.R.; Glasky, A.J.; Fick, D.B. (Spectrum Pharmaceuticals, Inc.); Tetrahydroindolone and purine derivs. linked to arylpiperazines. WO 0311396 .

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)	22114	1-(3-chlorophenyl)piperazine	6640-24-0	C₁₀H₁₃ClN₂	详情	详情
(II)	63473	1-(2-chloroethyl)-4-(3-chlorophenyl)piperazine		C₁₂H₁₆Cl₂N₂	详情	详情
(III)	63474	2-bromo-4-pyridinamine; 2-bromo-4-pyridinylamine		C₅H₅BrN₂	详情	详情

Extended Information