2-(2-Chlorophenyl)-4-(isopropylamino)-2-(2-piperidinoethyl)butanamide -Drug Synthesis Database

【结构式】

【分子编号】11438

【品名】2-(2-Chlorophenyl)-4-(isopropylamino)-2-(2-piperidinoethyl)butanamide

【CA登记号】

【分子式】C₂₀H₃₂ClN₃O

【分子量】365.9464

【元素组成】C 65.64% H 8.81% Cl 9.69% N 11.48% O 4.37%

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：(V)

The alkylation of the alpha-N-piperidinylethyl derivative of the 2-chlorophenylacetonitrile (I) with N-benzyl-N-isopropylaminoethyl chloride (II) (4) and sodium amide in refluxing toluene gives (rac)-alpha-(2-chlorophenyl)-alpha-[2-[(1-methylethyl)(phenylmethyl) amino]ethyl]-1-piperidinebutanenitrile (III). Hydration of the nitrile (III) with sulfuric acid provided (rac)-alpha-[1-[(1-methylethyl)(phenylmethyl)amino]ethyl]-1-piperidinebutanamide (IV), and subsequent catalytic hydrogenolysis of the N-benzyl group yielded (rac)-alpha-(2-chlorophenyl)-alpha-[(1-methylethyl)amino]ethyl] piperidinebutanamide (V). Final acylation of the secondary amine (V) with acetyl chloride in chloroform in the presence of triethylamine was carried out at 0 C to provide bidisomide (SC-40230).

参考文献中间体

合成目标

【1】 Desai, B.N.; Chorvat, R.J.; Rorig, K.J. (G.D. Searle & Co.); Monobasic derivatives of disobutamide. US 4639524 .
【2】 Novotney, R.L.; Woo, C.M.; Yonan, P.K.; Hershenson, F.; Prodan, K.A.; Synthesis and antiarrhythmic activity of alpha-bis[(dialkylamino)alkyl]phenylacetamides. J Med Chem 1980, 23, 10, 1102.
【3】 Chorvat, R.J.; Rorig, K.J.; Fowler, K.W.; Frederick, L.G.; Desai, B.N.; Garthwaite, S.M.; Hatley, F.R.; Synthesis and structure-activity relationships of new series of antiarrhythmic agents: Monobasic derivatives of disobutamide. J Med Chem 1988, 31, 2158.
【4】 Cook, C.S.; Claypool, W.D.Garthwaite, S.M.; Desai, B.N.; Bidisomide. Drugs Fut 1992, 17, 5, 374.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	11434	2-(2-Chlorophenyl)-4-piperidinobutanenitrile	C₁₅H₁₉ClN₂	详情	详情
(II)	11435	N-Benzyl-N-(2-chloroethyl)-2-propanamine; N-Benzyl-N-(2-chloroethyl)-N-isopropylamine	C₁₂H₁₈ClN	详情	详情
(III)	11436	4-[Benzyl(isopropyl)amino]-2-(2-chlorophenyl)-2-(2-piperidinoethyl)butanenitrile	C₂₇H₃₆ClN₃	详情	详情
(IV)	11437	4-[Benzyl(isopropyl)amino]-2-(2-chlorophenyl)-2-(2-piperidinoethyl)butanamide	C₂₇H₃₈ClN₃O	详情	详情
(V)	11438	2-(2-Chlorophenyl)-4-(isopropylamino)-2-(2-piperidinoethyl)butanamide	C₂₀H₃₂ClN₃O	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VIII)

The reaction of N-isopropylethanolamine (I) with allyl bromide (II) in THF gives the secondary amine (III), which is treated with SOCl2 in dichloromethane to yield the chloroethylamine (IV). The condensation of (IV) with 2-(2-chlorophenyl)-4-(1-piperidinyl)butyronitrile (V) by means of KOH in DMSO affords the adduct (VI), whose nitrile group is hydrolyzed with H2SO4 to provide the corresponding amide (VII). The elimination of the allyl group of (VII) by means of a Rh catalyst and 1,4-diazabicyclo[2,2,2]octane (DABCO) in refluxing aqueous ethanol gives the secondary amine (VIII), which is finally acetylated with Ac2O in ethyl acetate to yield the target diamide.

参考文献中间体

合成目标

【1】 Awasthi, A.K.; Paul, K.; A new and improved synthesis of bidisomide. Org Process Res Dev 2001, 5, 5, 528.

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)	51925	2-(Isopropylamino)ethanol; 2-(iso-Propylamino)ethanol; N-Isopropylethanolamine	109-56-8	C₅H₁₃NO	详情	详情
(II)	11463	3-Bromo-1-propene; 3-Bromopropene；allyl bromide	106-95-6	C₃H₅Br	详情	详情
(III)	51926	2-[allyl(isopropyl)amino]-1-ethanol		C₈H₁₇NO	详情	详情
(IV)	51927	N-(2-chloroethyl)-N-isopropyl-2-propen-1-amine; N-allyl-N-(2-chloroethyl)-N-isopropylamine		C₈H₁₆ClN	详情	详情
(V)	11434	2-(2-Chlorophenyl)-4-piperidinobutanenitrile		C₁₅H₁₉ClN₂	详情	详情
(VI)	51928	4-[allyl(isopropyl)amino]-2-(2-chlorophenyl)-2-[2-(1-piperidinyl)ethyl]butanenitrile		C₂₃H₃₄ClN₃	详情	详情
(VII)	51929	4-[allyl(isopropyl)amino]-2-(2-chlorophenyl)-2-[2-(1-piperidinyl)ethyl]butanamide		C₂₃H₃₆ClN₃O	详情	详情
(VIII)	11438	2-(2-Chlorophenyl)-4-(isopropylamino)-2-(2-piperidinoethyl)butanamide		C₂₀H₃₂ClN₃O	详情	详情

Extended Information