1-[(E)-3-bromo-1-propenyl]benzene -Drug Synthesis Database

【结构式】

【分子编号】21131

【品名】1-[(E)-3-bromo-1-propenyl]benzene

【CA登记号】4392-24-9

【分子式】C₉H₉Br

【分子量】197.07446

【元素组成】C 54.85% H 4.6% Br 40.55%

与该中间体有关的原料药合成路线共 4 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1

该中间体在本合成路线中的序号：(II)

1) Racemic igmesine has been synthesized as follows: Alkylation of 2-phenylbutyric acid (I) with cinnamyl bromide (II) by means of butyllithium in THF gives 2-ethyl-2,5-diphenyl-4-pentenoic acid (III), which is treated with sodium azide and phenyl dichlorophosphate in dichloromethane, yielding the corresponding azide (IV). The Curtius rearrangement of (IV) in refluxing toluene affords the isocyanate (V), which is reduced with LiAlH4/AlCl3 in THF to give N-(1-ethyl-1,4-diphenyl-3-butenyl)-N-metylamine (VI). The acylation of (VI) with cyclopropanecarbonyl chloride (VII) by means of triethylamine in dichloromethane yields the corresponding amide (VIII), which is finally reduced with LiAlH4/AlCl3 in THF/ethyl ether.

参考文献中间体

合成目标

【1】 Sorbera, L.A.; Castaner, J.; Silvestre, J.S.; Igmesine Hydrochloride . Drugs Fut 1999, 24, 2, 133.
【2】 Aubard, G.; Calvet, A.; Gouret, C.; Grouhel, A.; Jacobelli, H.; Junien, J.-L. (Jouveinal SA); Disubstituted benzylamines, process for their preparation, their use as medicament and their synthesis intermediates. EP 0361990; EP 0362001; FR 2636625; US 5034419; US 5089639 .

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)	21130	2-Phenylbutyric acid; alpha-Ethylbenzeneacetic acid	90-27-7	C₁₀H₁₂O₂	详情	详情
(II)	21131	1-[(E)-3-bromo-1-propenyl]benzene	4392-24-9	C₉H₉Br	详情	详情
(III)	21132	(E)-2-ethyl-2,5-diphenyl-4-pentenoic acid		C₁₉H₂₀O₂	详情	详情
(IV)	21133	(E)-2-ethyl-2,5-diphenyl-4-pentenoyl azide		C₁₉H₁₉N₃O	详情	详情
(V)	21134	1-[(E)-1-ethyl-1-isocyanato-4-phenyl-3-butenyl]benzene; (E)-1-ethyl-1,4-diphenyl-3-butenyl isocyanate		C₁₉H₁₉NO	详情	详情
(VI)	21135	(rac)-[(E)-N-methyl-3,6-diphenyl-5-hexen-3-amine]; (rac)-[N-[(E)-1-ethyl-1,4-diphenyl-3-butenyl]-N-methylamine]		C₁₉H₂₃N	详情	详情
(VII)	14061	Cyclopropanecarbonyl chloride; Cyclopropanecarboxylic acid chloride	4023-34-1	C₄H₅ClO	详情	详情
(VIII)	21137	(rac)-[N-[(E)-1-ethyl-1,4-diphenyl-3-butenyl]-N-methylcyclopropanecarboxamide]		C₂₃H₂₇NO	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

Synthesis of intermediate triphenylphosphonium salt (VII): The condensation of the chiral oxazolidinone (I) with cinnamyl bromide (II) by means of NaHMDS in THF gives the adduct (III), which is treated with LiBH4 in Et2O/water to yield the alcohol (IV). The protection of (IV) with Tbdms-Cl and imidazole in DMF affords the silyl ether (V), which is treated with ozone and reduced with NaBH4 to provide the alcohol (VI). The reaction of (VI) with I2 and PPh3 gives the desired triphenylphosphonium iodide (VII).

参考文献中间体

合成目标

【1】 Mulzer, J.; et al.; A novel highly stereoselective total synthesis of epothilone B and of its (12R,13R) acetonide. Tetrahedron Lett 2000, 41, 40, 7635.

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)	46163	(4R,5S)-4-methyl-5-phenyl-3-propionyl-1,3-oxazolidin-2-one		C₁₃H₁₅NO₃	详情	详情
(II)	21131	1-[(E)-3-bromo-1-propenyl]benzene	4392-24-9	C₉H₉Br	详情	详情
(III)	46164	(4R,5S)-4-methyl-3-[(2S,4E)-2-methyl-5-phenyl-4-pentenoyl]-5-phenyl-1,3-oxazolidin-2-one		C₂₂H₂₃NO₃	详情	详情
(IV)	46165	(2S,4E)-2-methyl-5-phenyl-4-penten-1-ol		C₁₂H₁₆O	详情	详情
(V)	46166	tert-butyl(dimethyl)silyl (2S,4E)-2-methyl-5-phenyl-4-pentenyl ether; tert-butyl(dimethyl)[[(2S,4E)-2-methyl-5-phenyl-4-pentenyl]oxy]silane		C₁₈H₃₀OSi	详情	详情
(VI)	46167	(3S)-4-[[tert-butyl(dimethyl)silyl]oxy]-3-methyl-1-butanol		C₁₁H₂₆O₂Si	详情	详情
(VII)	46168	((3S)-4-[[tert-butyl(dimethyl)silyl]oxy]-3-methylbutyl)(triphenyl)phosphonium iodide		C₂₉H₄₀IOPSi	详情	详情

合成路线3

该中间体在本合成路线中的序号：(V)

(R)-2-Bromo-4-methylpentanoic acid (I) was protected as the benzyl ester (II) and subsequently condensed with benzyl tert-butyl malonate (III) in the presence of potassium tert-butoxide to furnish the triester (IV) as an epimeric mixture. Alkylation of (IV) with cinnamyl bromide (V) produced adduct (VI). The key intermediate (VII) was then obtained by catalytic hydrogenation of the benzyl esters and olefin double bond of (VI), followed by thermal malonate decarboxylation.

参考文献中间体

合成目标

【1】 Fujisawa, T.; Odake, S.; Morita, Y.; Hongo, T.; Ito, H.; Yasuda, J.; Suda, E.; Igeta, K.; Morikawa, T. (Fuji Yakuhin Kogyo Co., Ltd.); Highly water-soluble metalloproteinase inhibitor. EP 0832875; WO 9633968 .

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)	26058	(2S)-2-bromo-4-methylpentanoic acid		C₆H₁₁BrO₂	详情	详情
(II)	60695	benzyl (2R)-2-bromo-4-methylpentanoate		C₁₃H₁₇BrO₂	详情	详情
(III)	60696	1-benzyl 3-(tert-butyl) malonate		C₁₄H₁₈O₄	详情	详情
(IV)	60697	1,2-dibenzyl 1-(tert-butyl) (2R)-4-methyl-1,1,2-pentanetricarboxylate		C₂₇H₃₄O₆	详情	详情
(V)	21131	1-[(E)-3-bromo-1-propenyl]benzene	4392-24-9	C₉H₉Br	详情	详情
(VI)	60698	4,5-dibenzyl 4-(tert-butyl) (E,5R)-7-methyl-1-phenyl-1-octene-4,4,5-tricarboxylate		C₃₆H₄₂O₆	详情	详情
(VII)	60699	(2R)-3-(tert-butoxycarbonyl)-2-isobutyl-6-phenylhexanoic acid		C₂₁H₃₂O₄	详情	详情

合成路线4

该中间体在本合成路线中的序号：(II)

Alkylation of 14-hydroxycodeinone (I) with cinnamyl bromide (II) in the presence of NaH in DMF gives 14-cinnamyloxycodeinone (III). Catalytic hydrogenation of (III) over Pd/C catalyst affords the corresponding 7,8-dihydro-14-phenylpropoxy derivative (IV). N-Demethylation of (IV) is accomplished by treatment with 1-chloroethyl chloroformate, followed by cleavage of the intermediate chloroethyl carbamate in refluxing MeOH. The resulting N-nor derivative (V) is then alkylated with allyl bromide (VI) using K2CO3 in DMF to provide the N-allyl amine (VII). O-Demethylation of (VII) with boiling 48% HBr yields phenol (VIII). Finally, catalytic hydrogenation of the N-allyl group of (VIII) in the presence of Pd/C affords the title N-propyl derivative.

参考文献中间体

合成目标

【1】 Greiner, E.; Spetea, M.; Krassnig, R.; Schullner, F.; Aceto, M.; Harris, L.S.; Traynor, J.R.; Woods, J.H.; Coop, A.; Schmidhammer, H.; Synthesis and biological evaluation of 14-alkoxymorphinans. 18.(1) N-substituted 14-phenylpropyloxymorphinan-6-ones with unanticipated agonist properties: Extending the scope of common structure-activity relationships. J Med Chem 2003, 46, 9, 1758.

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)	64962	17-hydroxy-4-methyl-10-(methyloxy)-12-oxa-4-azapentacyclo[9.6.1.0~1,13~.0~5,17~.0~7,18~]octadeca-7(18),8,10,15-tetraen-14-one		C₁₈H₁₉NO₄	详情	详情
(II)	21131	1-[(E)-3-bromo-1-propenyl]benzene	4392-24-9	C₉H₉Br	详情	详情
(III)	64963			C₂₇H₂₇NO₄	详情	详情
(IV)	64964			C₂₇H₃₁NO₄	详情	详情
(V)	64965			C₂₆H₂₉NO₄	详情	详情
(VI)	11463	3-Bromo-1-propene; 3-Bromopropene；allyl bromide	106-95-6	C₃H₅Br	详情	详情
(VII)	64966			C₂₉H₃₃NO₄	详情	详情
(VIII)	64967			C₂₈H₃₁NO₄	详情	详情

Extended Information