1-[(E)-2-phenylethenyl]pyrrolidine -Drug Synthesis Database

【结构式】

【分子编号】46508

【品名】1-[(E)-2-phenylethenyl]pyrrolidine

【CA登记号】

【分子式】C₁₂H₁₅N

【分子量】173.25784

【元素组成】C 83.19% H 8.73% N 8.08%

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：(XI)

The reaction of the prostaglandin E1 derivative (I) with N,S-dimethylphenylsulfonimide (II) by means of methylmagnesium chloride in THF gives intermediate (III), which is treated with aluminum amalgam in HOAc/water to yield the methylene derivative (IV). Hydroboration of (IV) with 9-borabicyclo[3.3.1]nonane (9-BBN) in THF affords the hydroxymethyl derivative (V), which is treated with methanesulfonyl chloride and TEA in dichloromethane to provide mesylate (VI). Desilylation of compound (VI) with TBAF in THF gives the phenol derivative (VII), which is cyclized by means of NaH in THF yielding the tricyclic prostaglandin derivative (VIII). Alkylation of compound (VIII) with methyl bromoacetate (IX) by means of NaH in glyme affords the 2-hydroxyacetate derivative (X), which is treated first with HOAc/water in order to eliminate the THP protecting groups, and then with KOH in methanol/water to hydrolyze the methyl ester group providing the prostaglandin F1 derivative (XI). Finally, this compound is hydrogenated over Pd/C in ethyl acetate.

参考文献中间体

合成目标

【1】 Sorbera, L.A.; Castaner, J.; Rabasseda, X.; UT-15. Drugs Fut 2001, 26, 4, 364.
【2】 Aristoff, P.A.; Kelly, R.C.; Nelson, N.A. (Pharmacia Corp.); Carbacyclin analogues. CH 648017; CH 655308; FR 2484413; GB 2070596; JP 1990167248; JP 1994145085 .
【3】 Aristoff, P.A. (Pharmacia Corp.); Methano carbacyclin analogs. US 4349689 .
【4】 Agoh, Y.; Agoh, M.; Tamura, T.; Kuriyama, H.; Soga, M.; Mori, T. (Maruishi Pharmaceutical Co., Ltd.); 1,2-Disubstd. 1,4-dihydro-4-oxoquinoline cpds.. EP 1081138; JP 2001064259; JP 2001064261; JP 2001089455; JP 2001089476 .

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)	46549	(2R,3R,4R)-2-(3-[[tert-butyl(dimethyl)silyl]oxy]benzyl)-4-(tetrahydro-2H-pyran-2-yloxy)-3-[(E,3S)-3-(tetrahydro-2H-pyran-2-yloxy)-1-octenyl]cyclopentanone		C₃₆H₅₈O₆Si	详情	详情
(II)	46550	methyl(methylimino)oxo(phenyl)-lambda(6)-sulfane		C₈H₁₁NOS	详情	详情
(III)	46551	tert-butyl(dimethyl)[3-([(1R,2R,3R)-5-[[methyl(phenyl)sulfonimidoyl]methyl]-3-(tetrahydro-2H-pyran-2-yloxy)-2-[(E,3S)-3-(tetrahydro-2H-pyran-2-yloxy)-1-octenyl]cyclopentyl]methyl)phenoxy]silane		C₄₄H₆₉NO₆SSi	详情	详情
(IV)	46552	tert-butyl(dimethyl)silyl 3-([(1R,2R,3R)-5-methylene-3-(tetrahydro-2H-pyran-2-yloxy)-2-[(E,3S)-3-(tetrahydro-2H-pyran-2-yloxy)-1-octenyl]cyclopentyl]methyl)phenyl ether; tert-butyl(dimethyl)[3-([(1R,2R,3R)-5-methylene-3-(tetrahydro-2H-pyran-2-yloxy)-2-[(E,3S)-3-(tetrahydro-2H-pyran-2-yloxy)-1-octenyl]cyclopentyl]methyl)phenoxy]silane		C₃₇H₆₀O₅Si	详情	详情
(V)	46553	[(1S,2S,3S,4R)-2-(3-[[tert-butyl(dimethyl)silyl]oxy]benzyl)-4-(tetrahydro-2H-pyran-2-yloxy)-3-[(E,3S)-3-(tetrahydro-2H-pyran-2-yloxy)-1-octenyl]cyclopentyl]methanol		C₃₇H₆₂O₆Si	详情	详情
(VI)	46554	[(1S,2S,3S,4R)-2-(3-[[tert-butyl(dimethyl)silyl]oxy]benzyl)-4-(tetrahydro-2H-pyran-2-yloxy)-3-[(E,3S)-3-(tetrahydro-2H-pyran-2-yloxy)-1-octenyl]cyclopentyl]methyl methanesulfonate		C₃₈H₆₄O₈SSi	详情	详情
(VII)	46555	[(1S,2S,3S,4R)-2-(3-hydroxybenzyl)-4-(tetrahydro-2H-pyran-2-yloxy)-3-[(E,3S)-3-(tetrahydro-2H-pyran-2-yloxy)-1-octenyl]cyclopentyl]methyl methanesulfonate		C₃₂H₅₀O₈S	详情	详情
(VIII)	46556	(1S,2R,3aS,9aS)-2-(tetrahydro-2H-pyran-2-yloxy)-1-[(E,3S)-3-(tetrahydro-2H-pyran-2-yloxy)-1-octenyl]-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]naphthalen-5-ol		C₃₁H₄₆O₅	详情	详情
(IX)	12309	methyl 2-bromoacetate; methyl bromoacetate	96-32-2	C₃H₅BrO₂	详情	详情
(X)	46507	3-bromo-6-phenyl-2-pyrazinecarbonitrile		C₁₁H₆BrN₃	详情	详情
(XI)	46508	1-[(E)-2-phenylethenyl]pyrrolidine		C₁₂H₁₅N	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XX)

In an alternative synthesis, phenylacetaldehyde (XVIII) was condensed with pyrrolidine (XIX) to give enamine (XX). Nitrosation of malononitrile (XXI), followed by treatment with tosyl chloride, produced the O-tosyl oxime (XXII). This was condensed with enamine (XX), and to the intermediate adduct (XXIII) was added thiophenol producing the phenylthiopyrazine (XXIV). Subsequent oxidation of the sulfide group of (XXIV) to sulfone (XXV), followed by condensation with methyl thioglycolate, gave the desired thienopyrazine (XIII).

参考文献中间体

合成目标

【1】 Meyer, M.D.; Altenbach, R.J.; Basha, F.; Carroll, W.A.; Drizin, I.; Kerwin, J.F.; Wendt, M.D.; Haight, A.R.; Zhang, W. (Abbott Laboratories Inc.); Benzopyranopyrrole and benzopyranopyridine alpha-1 adrenergic cpds.. EP 0942911; US 5891882; US 6046207; WO 9824791 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XIII)	46503	methyl 7-amino-2-phenylthieno[2,3-b]pyrazine-6-carboxylate		C₁₄H₁₁N₃O₂S	详情	详情
(XVIII)	18456	2-phenylacetaldehyde	122-78-1	C₈H₈O	详情	详情
(XIX)	11376	Pyrrolidine	123-75-1	C₄H₉N	详情	详情
(XX)	46508	1-[(E)-2-phenylethenyl]pyrrolidine		C₁₂H₁₅N	详情	详情
(XXI)	12061	Malononitrile	109-77-3	C₃H₂N₂	详情	详情
(XXII)	46509	2-([[(4-methylphenyl)sulfonyl]oxy]imino)malononitrile		C₁₀H₇N₃O₃S	详情	详情
(XXIII)	46510	2-[[(E)-1-phenyl-2-(1-pyrrolidinyl)ethenyl]imino]malononitrile		C₁₅H₁₄N₄	详情	详情
(XXIV)	46511	6-phenyl-3-(phenylsulfanyl)-2-pyrazinecarbonitrile		C₁₇H₁₁N₃S	详情	详情
(XXV)	46512	6-phenyl-3-(phenylsulfonyl)-2-pyrazinecarbonitrile		C₁₇H₁₁N₃O₂S	详情	详情

Extended Information