1-(3-chloropropyl)-4-(4-fluorophenyl)piperazine -Drug Synthesis Database

【结构式】

【分子编号】45622

【品名】1-(3-chloropropyl)-4-(4-fluorophenyl)piperazine

【CA登记号】

【分子式】C₁₃H₁₈ClFN₂

【分子量】256.7505032

【元素组成】C 60.82% H 7.07% Cl 13.81% F 7.4% N 10.91%

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：(IX)

Treatment of methyl pyrrole-2-carboxylate (I) with KOtBu and 18-crown-6 in Et2O, followed by reaction with ethyl iodide (II) in Et2O, yields methyl 1-ethylpyrrole-2-carboxylate (III), which is then subjected to saponification with NaOH to afford carboxylic acid (IV). Condensation of (IV) with beta-alanine benzyl ester p-toluene sulfonate (V) in the presence of diethyl phosphorocyanidate (DEPC) and Et3N in DMF provides benzyl ester (VI), which is then hydrogenated over Pd/C in THF, furnishing carboxylic acid (VII). Cyclization of (VII) with polyphosphoric acid (PPA) affords derivative (VIII), which is then treated with NaH in DMF and alkylated with chloro derivative (IX) in DMF to produce compound (X). Finally, treatment of (X) with hydroxylamine hydrochloride and NaOAc affords the target compound.

参考文献中间体

合成目标

【1】 Mizuno, A.; Miya, M.; Inomata, N.; Tatsuoka, T.; Ishihara, T. (Suntory Ltd.); Pyrroloazepine cpd.. EP 0557526; JP 1993503481; US 5399557; WO 9303032 .
【2】 Yamaki, A.; Tatsuoka, T.; Miya, M.; Nakanishi, K.; Mizuno, A.; Takiguchi, C.; Hidaka, T.; Kamei, T.; Shibata, M.; Inomata, N.; Studies on antihypertensive agents with antithrombotic activity. 2. Syntheses and pharmacological evaluation of pyrrolo[2,3-c]azepine derivatives. Chem Pharm Bull 2000, 48, 8, 1129.

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)	45616	methyl 1H-pyrrole-2-carboxylate		C₆H₇NO₂	详情	详情
(II)	10925	Iodoethane;ethyl iod	75-03-6	C₂H₅I	详情	详情
(III)	45617	methyl 1-ethyl-1H-pyrrole-2-carboxylate		C₈H₁₁NO₂	详情	详情
(IV)	45618	1-ethyl-1H-pyrrole-2-carboxylic acid		C₇H₉NO₂	详情	详情
(V)	30194	benzyl 3-aminopropanoate	27019-47-2	C₁₀H₁₃NO₂	详情	详情
(VI)	45619	benzyl 3-[[(1-ethyl-1H-pyrrol-2-yl)carbonyl]amino]propanoate		C₁₇H₂₀N₂O₃	详情	详情
(VII)	45620	N-[(1-ethyl-1H-pyrrol-2-yl)carbonyl]-beta-alanine		C₁₀H₁₄N₂O₃	详情	详情
(VIII)	45621	1-ethyl-6,7-dihydropyrrolo[2,3-c]azepine-4,8(1H,5H)-dione		C₁₀H₁₂N₂O₂	详情	详情
(IX)	45622	1-(3-chloropropyl)-4-(4-fluorophenyl)piperazine		C₁₃H₁₈ClFN₂	详情	详情
(X)	45623	1-ethyl-7-[3-[4-(4-fluorophenyl)-1-piperazinyl]propyl]-6,7-dihydropyrrolo[2,3-c]azepine-4,8(1H,5H)-dione		C₂₃H₂₉FN₄O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

The title compound was synthesized by two related methods. 2-Pyrrolidone (I) was alkylated with 1-bromo-3-chloropropane (II) using either sodium or potassium metal or potassium tert-butoxide as the base. The resultant N-(3-chloropropyl)pyrrolidone (III) was then condensed with 1-(4-fluorophenyl)piperazine (IV) in the presence of NaI and Na2CO3 to produce the desired disubstituted piperazine. Alternatively, the title compound was prepared from the known N-(3-chloropropyl)-N'-(4-fluorophenyl)piperazine (V) by condensation with 2-pyrrolidone (I) in the presence of sodium metal in hot xylene.

参考文献中间体

合成目标

【2】 Jain, S.; Sinha, N.; Saxena, A.K.; Anand, N.; Saxena, R.M.; Dubey, M.P.; Patnaik, G.K.; Ray, M. (Council of Scientific and Industrial Research); Methods for preparing 1-[4-arylpiperazin-1-yl]-3-[2-oxopyrrolidin/piperidin-1-yl]propanes. US 6084097 .
【1】 Jain, S.; Sinha, N.; Saxena, A.K.; Anand, N.; Saxena, R.M.; Dubey, M.P.; Patnaik, G.K.; Ray, M. (Council of Scientific and Industrial Research); 1-[4-Arylpiperazin-1-yl]-3-[2-oxopyrrolidin/piperidin-1-yl]propanes and their use in medical treatments. US 6150367 .

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)	27397	2-Pyrrolidinone	616-45-5	C₄H₇NO	详情	详情
(II)	10358	1-Bromo-3-chloropropane	109-70-6	C₃H₆BrCl	详情	详情
(III)	52874	1-(3-chloropropyl)-2-pyrrolidinone		C₇H₁₂ClNO	详情	详情
(IV)	12143	1-(4-Fluorophenyl)piperazine	2252-63-3	C₁₀H₁₃FN₂	详情	详情
(V)	27397	2-Pyrrolidinone	616-45-5	C₄H₇NO	详情	详情
(VI)	45622	1-(3-chloropropyl)-4-(4-fluorophenyl)piperazine		C₁₃H₁₈ClFN₂	详情	详情

Extended Information