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【结 构 式】

【分子编号】46549

【品名】(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

【CA登记号】

【 分 子 式 】C36H58O6Si

【 分 子 量 】614.93842

【元素组成】C 70.32% H 9.51% O 15.61% Si 4.57%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(I)

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.

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:(VI)

 

1 Aristoff PA. 1987. Interphenylene carbacyclin derivatives. US 4683330(本专利属于The Upjohn Compa- ny) Aristoff PA 1981.Composition and pro卧US 4306075(本专利■于The Upjohn Company) Aristoff PA. 1982,Methno carbacyclin analogs US 4349689(本专利属于The Upjohn Company)
2 Aristoff PA. 1981.Composition and process. US 4306075(本专利属于The Upjohn Company)
3 Aristoff PA. 1982. Methno carbacyclin analogs. US 4349689(本专利属于The Upjohn Company)
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) 14647 5-methoxy-3,4-dihydro-2(1H)-naphthalenone 32940-15-1 C11H12O2 详情 详情
(II) 46567 (3aS)-5-methoxy-3a,4-dihydronaphtho[2,3-b]furan-2(3H)-one C13H12O3 详情 详情
(III) 46566 dimethyl (4S)-4-(tetrahydro-2H-pyran-2-yloxy)nonylphosphonate C16H33O5P 详情 详情
(IV) 46568 (9aS)-8-methoxy-3-[(3S)-3-(tetrahydro-2H-pyran-2-yloxy)octyl]-1,4,9,9a-tetrahydro-2H-cyclopenta[b]naphthalen-2-one C27H38O4 详情 详情
(VI) 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
(VII) 66890 2-(3-((tert-butyldimethylsilyl)oxy)benzyl)-1-((N-methylphenylsulfonimidoyl)methyl)-4-((tetrahydro-2H-pyran-2-yl)peroxy)-3-(3-((tetrahydro-2H-pyran-2-yl)peroxy)octyl)cyclopentanol   C44H71NO9SSi 详情 详情
(VIII) 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
(IX) 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
Extended Information