1-bromo-3-methylbutane -Drug Synthesis Database

【结构式】

【分子编号】46234

【品名】1-bromo-3-methylbutane

【CA登记号】

【分子式】C₅H₁₁Br

【分子量】151.04634

【元素组成】C 39.76% H 7.34% Br 52.9%

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：(II)

Wittig reaction between aldehyde (I) and bromo derivative (II) by means of triethyl phosphonoacetate and NaH in 1,2-dimethoxyethane (A) affords a mixture of isomeric acrylates (IIIa-b), which are hydrogenated over Pd/C in EtOH to yield derivative (IV). Hydrolysis of ethyl ester (IV) by means of KOH or NaOH provides carboxylic acid (V), which is then converted into N-protected derivative (VI) by first treatment with diphenylphosphoryl azide (DPPA) and Et3N in refluxing benzene, followed by reaction with refluxing t-butanol. Boc removal of (VI) with TFA in CH2Cl2 furnishes free amine (VII), which is finally alkylated with propyl bromide (VIII) by means of K2CO3 in DMF to yield the target product.

参考文献中间体

合成目标

【1】 Tomisawa, K.; Ohta, K.; Nakazato, A.; Kumagai, T.; Chaki, S.; Okuyama, S.; Synthesis and SAR of 1-alkyl-2-phenylethylamine derivatives designed from N,N-dipropyl-4-methoxy-3-(2-phenylethoxy)phenylethylamine to discover sigma1 ligands. J Med Chem 1999, 42, 19, 3965.
【2】 Nakazato, A.; Kumagai, T.; Miyazawa, T.; Ohta, K.; Kawashima, Y.; Hatayama, K. (Taisho Pharmaceutical Co., Ltd.); Optically active substd. phenylalkylamine derivs.. EP 0870758; JP 1997059230; US 5990151; WO 9700238 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	10019	Ethyl 2-(diethoxyphosphoryl)acetate; Triethyl phosphonoacetate	867-13-0	C₈H₁₇O₅P	详情	详情
(IIIa)	46235	ethyl (Z)-2-isopentyl-3-[4-methoxy-3-(phenethyloxy)phenyl]-2-propenoate		C₂₅H₃₂O₄	详情	详情
(IIIb)	46236	ethyl (E)-2-isopentyl-3-[4-methoxy-3-(phenethyloxy)phenyl]-2-propenoate		C₂₅H₃₂O₄	详情	详情
(I)	23679	4-methoxy-3-(phenethyloxy)benzaldehyde		C₁₆H₁₆O₃	详情	详情
(II)	46234	1-bromo-3-methylbutane		C₅H₁₁Br	详情	详情
(IV)	46237	ethyl 2-[4-methoxy-3-(phenethyloxy)benzyl]-5-methylhexanoate		C₂₅H₃₄O₄	详情	详情
(V)	46238	2-[4-methoxy-3-(phenethyloxy)benzyl]-5-methylhexanoic acid		C₂₃H₃₀O₄	详情	详情
(VI)	46239	tert-butyl 1-[4-methoxy-3-(phenethyloxy)benzyl]-4-methylpentylcarbamate		C₂₇H₃₉NO₄	详情	详情
(VII)	46240	1-[4-methoxy-3-(phenethyloxy)benzyl]-4-methylpentylamine; 1-[4-methoxy-3-(phenethyloxy)phenyl]-5-methyl-2-hexanamine		C₂₂H₃₁NO₂	详情	详情
(VIII)	19502	Propyl bromide; 1-Bromopropane	106-94-5	C₃H₇Br	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

Alkylation of ethyl 4-nitropyrrole-2-carboxylate (I) with 3-methylbutyl bromide (II) in the presence of NaOMe affords the N-isoamyl pyrrole (III). Saponification of the ethyl ester group of (III), followed by treatment of the resultant carboxylic acid (IV) with SOCl2 provides acid chloride (V). This is subsequently coupled with 3-aminopropionitrile (VI) to yield the N-(2-cyanoethyl) amide (VII). Conversion of the cyano group of (VII) into the N-methyl amidine (VIII) is then accomplished under Pinner reaction conditions. Reduction of the nitro group of (VIII) by catalytic hydrogenation over Pd/C furnishes the intermediate aminopyrrole (IX).

参考文献中间体

合成目标

【1】 Roberts, C.D.; Keicher, J.D.; Dyatkina, N.B.; et al.; Minor groove DNA binders as antimicrobial agents. 1. Pyrrole tetraamides are potent antibacterials against vancomycin resistant Enteroccoci and methicillin resistant Staphylococcus aureus. J Med Chem 2002, 45, 4, 805.
【2】 Dyatkina, N.; Hanson, E.; Liehr, S.; et al.; Synthesis, SAR and antimicrobial activity of pyrrole tetraamides. 224th ACS Natl Meet (Aug 18 2002, Boston) 2002, Abst MEDI 62.
【3】 Nelson, P.H.; Muchowski, J.M.; Dyatkina, N.B.; Shi, D.-F.; Zhang, W.; Liehr, S.J.R.; Velligan, M.D.; Botyanszki, J.; Roberts, C.D.; Khorlin, A. (Genelabs Technologies, Inc.); Novel cpds. possessing antibacterial, antifungal or antitumor activity. WO 0200650 .

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)	60988	1-methoxy-2,3-dihydro-1H-inden-2-yl methanesulfonate		C₁₁H₁₄O₄S	详情	详情
(II)	46234	1-bromo-3-methylbutane		C₅H₁₁Br	详情	详情
(III)	54019	ethyl 1-isopentyl-4-nitro-1H-pyrrole-2-carboxylate		C₁₂H₁₈N₂O₄	详情	详情
(IV)	54020	1-isopentyl-4-nitro-1H-pyrrole-2-carboxylic acid		C₁₀H₁₄N₂O₄	详情	详情
(V)	54021	1-isopentyl-4-nitro-1H-pyrrole-2-carbonyl chloride		C₁₀H₁₃ClN₂O₃	详情	详情
(VI)	38094	3-aminopropanenitrile	151-18-8	C₃H₆N₂	详情	详情
(VII)	54022	N-(2-cyanoethyl)-1-isopentyl-4-nitro-1H-pyrrole-2-carboxamide		C₁₃H₁₈N₄O₃	详情	详情
(VIII)	60999	N-[3-imino-3-(methylamino)propyl]-1-isopentyl-4-nitro-1H-pyrrole-2-carboxamide		C₁₄H₂₃N₅O₃	详情	详情
(IX)	61000	4-amino-N-[3-imino-3-(methylamino)propyl]-1-isopentyl-1H-pyrrole-2-carboxamide		C₁₄H₂₅N₅O	详情	详情

Extended Information