4-bromobutanenitrile -Drug Synthesis Database

【结构式】

【分子编号】34789

【品名】4-bromobutanenitrile

【CA登记号】5332-06-9

【分子式】C₄H₆BrN

【分子量】148.00238

【元素组成】C 32.46% H 4.09% Br 53.99% N 9.46%

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：(XVI)

The condensation between 4-bromobutyronitrile (XVI) and 3-amino-1-propanol (XVII) gave the hydroxy amino nitrile (XVIII), which was further converted to the N,O-bis-tosylated derivative (XIX). Displacement of the tosylate ester group of (XIX) with NaI in boiling acetone afforded the alkyl iodide (XX). Alkylation of amine (XV) with iodide (XX) provided the secondary amine adduct (XXI). The p-toluenesulfonamido group of (XXI) was reductively removed by sodium in liquid ammonia, yielding diamine (XXII). Subsequent nitrile reduction by means of LiAlH4 furnished triamine (XXIII).

参考文献中间体

合成目标

【1】 Moriarty, R.M.; et al.; Synthesis of squalamine. A steroidal antibiotic from the shark. Tetrahedron Lett 1994, 35, 44, 8103.
【2】 Moriarty, R.M.; Guo, L.; Tuladhar, S.M. (Genaera Corp.); Chemical synthesis of squalamine. WO 9419366 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XV)	53701	(3S,5R,7R,8R,9S,10S,13R,14S,17R)-3-amino-17-((1R)-4-{[tert-butyl(dimethyl)silyl]oxy}-1,5-dimethylhexyl)-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-7-ol	n/a	C₃₃H₆₃NO₂Si	详情	详情
(XVI)	34789	4-bromobutanenitrile	5332-06-9	C₄H₆BrN	详情	详情
(XVII)	18522	3-amino-1-propanol	156-87-6	C₃H₉NO	详情	详情
(XVIII)	53702	4-[(3-hydroxypropyl)amino]butanenitrile	n/a	C₇H₁₄N₂O	详情	详情
(XIX)	53703	3-{(3-cyanopropyl)[(4-methylphenyl)sulfonyl]amino}propyl 4-methylbenzenesulfonate	n/a	C₂₁H₂₆N₂O₅S₂	详情	详情
(XX)	53704	N-(3-cyanopropyl)-N-(3-iodopropyl)-4-methylbenzenesulfonamide	n/a	C₁₄H₁₉IN₂O₂S	详情	详情
(XXI)	53705	N-(3-{[(3S,5R,7R,8R,9S,10S,13R,14S,17R)-17-((1R)-4-{[tert-butyl(dimethyl)silyl]oxy}-1,5-dimethylhexyl)-7-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-3-yl]amino}propyl)-N-(3-cyanopropyl)-4-methylbenzenesulfonamide	n/a	C₄₇H₈₁N₃O₄SSi	详情	详情
(XXII)	53706	4-[(3-{[(3S,5R,7R,8R,9S,10S,13R,14S,17R)-17-((1R)-4-{[tert-butyl(dimethyl)silyl]oxy}-1,5-dimethylhexyl)-7-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-3-yl]amino}propyl)amino]butanenitrile	n/a	C₄₀H₇₅N₃O₂Si	详情	详情
(XXIII)	53707	(3S,5R,7R,8R,9S,10S,13R,14S,17R)-3-({3-[(4-aminobutyl)amino]propyl}amino)-17-((1R)-4-{[tert-butyl(dimethyl)silyl]oxy}-1,5-dimethylhexyl)-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-7-ol	n/a	C₄₀H₇₉N₃O₂Si	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

N-(2-Methoxyphenyl)piperazine (I) was alkylated with 4-bromobutyronitrile (II) to provide the 3-cyanopropylpiperazine (III). Subsequent reduction of the cyano group of (III) using LiAlH4 produced the primary amine (IV). The title amide was then obtained by condensation of (IV) with 2-naphthoic acid (V) after activation as the corresponding acid chloride with (COCl)2 or as the mixed anhydride with isobutyl chloroformate.

参考文献中间体

合成目标

【1】 Mann, A.; Sokoloff, P.; Schwartz, J.-C.; Wermuth, C.-G.; Garrido, F.; Lecomte, J.-M. (INSERM (Institut National de la Sante et de la Recherche Medicale); Societe Civile Bioprojet); 2-Naphthamide derivs. and their therapeutic applications. EP 0779284; FR 2742149; US 5872119; US 5985895 .

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)	11882	1-(2-Methoxyphenyl)piperazine; Methyl 2-piperazinophenyl ether; 1-(2-Methoxyphenyl)-piperazine	35386-24-4	C₁₁H₁₆N₂O	详情	详情
(II)	34789	4-bromobutanenitrile	5332-06-9	C₄H₆BrN	详情	详情
(III)	34790	4-[4-(2-methoxyphenyl)-1-piperazinyl]butanenitrile		C₁₅H₂₁N₃O	详情	详情
(IV)	34791	4-[4-(2-methoxyphenyl)-1-piperazinyl]butylamine; 4-[4-(2-methoxyphenyl)-1-piperazinyl]-1-butanamine		C₁₅H₂₅N₃O	详情	详情
(V)	34792	2-naphthoic acid	93-09-4	C₁₁H₈O₂	详情	详情

合成路线3

该中间体在本合成路线中的序号：(II)

Alkylation of N-ethyl mesitylenesulfonamide (I) with 4-bromobutyronitrile (II) in the presence of NaH afforded the cyano sulfonamide (III). After catalytic hydrogenation of the cyano group of (III), the resulting amine (IV) was acylated with mesitylenesulfonyl chloride (V) to give the bis-sulfonamide (VI) (1). Subsequent condensation of (VI) with the bis-sulfonate (VII) produced the tetra-sulfonamide (VIII). Finally, cleavage of the mesitylenesulfonyl protecting groups of (VIII) using HBr in HOAc furnished the corresponding tetraamine, which was isolated as the hydrochloride salt.

参考文献中间体

合成目标

【2】 Marton, L.J.; Frydman, B. (SLIL Biomedical Corp.); Novel polyamine analog conjugates and quinone conjugates as therapies for cancers and prostate diseases. WO 0066175 .
【1】 Sarkar, A.; Basu, H.S.; Marton, L.J.; Valasinas, A.; Frydman, B.; Reddy, V.K.; Conformationally restricted analogues of 1N,14N-bisethylhomospermine (BE-4-4-4): Synthesis and growth inhibitory effects on human prostate cancer cells. J Med Chem 2001, 44, 3, 390.

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)	46925	N-ethyl-2,4,6-trimethylbenzenesulfonamide		C₁₁H₁₇NO₂S	详情	详情
(II)	34789	4-bromobutanenitrile	5332-06-9	C₄H₆BrN	详情	详情
(III)	46926	N-(3-cyanopropyl)-N-ethyl-2,4,6-trimethylbenzenesulfonamide		C₁₅H₂₂N₂O₂S	详情	详情
(IV)	46927	N-(4-aminobutyl)-N-ethyl-2,4,6-trimethylbenzenesulfonamide		C₁₅H₂₆N₂O₂S	详情	详情
(V)	41158	2,4,6-trimethylbenzenesulfonyl chloride	773-64-8	C₉H₁₁ClO₂S	详情	详情
(VI)	46928	N-ethyl-N-[4-[(mesitylsulfonyl)amino]butyl]-2,4,6-trimethylbenzenesulfonamide		C₂₄H₃₆N₂O₄S₂	详情	详情
(VII)	46929	((1R,2R)-2-[[(mesitylsulfonyl)oxy]methyl]cyclopropyl)methyl 2,4,6-trimethylbenzenesulfonate		C₂₃H₃₀O₆S₂	详情	详情
(VIII)	46930	N-ethyl-N-[4-[[((1R,2R)-2-[[[4-[ethyl(mesitylsulfonyl)amino]butyl](mesitylsulfonyl)amino]methyl]cyclopropyl)methyl](mesitylsulfonyl)amino]butyl]-2,4,6-trimethylbenzenesulfonamide		C₅₃H₇₈N₄O₈S₄	详情	详情

Extended Information