【结 构 式】 |
【分子编号】46550 【品名】methyl(methylimino)oxo(phenyl)-lambda(6)-sulfane 【CA登记号】 |
【 分 子 式 】C8H11NOS 【 分 子 量 】169.24748 【元素组成】C 56.77% H 6.55% N 8.28% O 9.45% S 18.95% |
合成路线1
该中间体在本合成路线中的序号:(II)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 |