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【结 构 式】

【分子编号】28364

【品名】5,7-difluoro-3,4-dihydro-2(1H)-naphthalenone

【CA登记号】

【 分 子 式 】C10H8F2O

【 分 子 量 】182.1697264

【元素组成】C 65.93% H 4.43% F 20.86% O 8.78%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(IV)

The reaction of 3,5-difluorophenylacetic acid with SOCl2 gives the corresponding acyl chloride (II), which is cyclized with ethylene (III) by means of AlCl3 in dichloromethane yielding the tetralone (IV). The stereoselective reduction of (IV) with LiAlH4 catalyzed by (1R,2S)-N-methylephedrine affords 5,7-difluoro-1,2,3,4-tetrahydro-2(R)-naphthol (V). The reaction of (V) with methanesulfonyl chloride and triethylamine gives the expected mesylate (VI), which is treated with LiN3 in DMF yielding the 2(S)-azide (VII). The reduction of (VII) with H2 over Pd/C in ethyl acetate affords the corresponding amine (VIII), which is treated with formaldehyde and KCN to give the 2-aminoacetonitrile (IX). The acylation of (IX) with butyl formate in refluxing acetonitrile yields the formamide (X), with is treated with ethyl formate and potassium tert-butoxide in THF to afford the hydroxyvinyl derivative (XI). The cyclization of (XI) with potassium thiocyanate in hot ethanol gives 1-(5,7-difluoro-1,2,3,4-tetrahydro naphthalen-2(S)-yl)-2-thioxo-2,3-dihydro-1H-imidazole-5-carbonitrile (XII), which is finally reduced with LiAlH4 in THF.

1 Martinez, G.R.; Repke, D.B.; Teitelbaum, P.J.; Walker, K.A.M.; Gooding, O.W.; Whiting, R.L.; Bansal, R.P.; Muehldorf, A.V. (Syntex (USA), Inc.); Benzocycloalkylazolethione derivs.. JP 1997512269; US 5438150; WO 9529165 .
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) 28361 2-(3,5-difluorophenyl)acetic acid 105184-38-1 C8H6F2O2 详情 详情
(II) 28362 2-(3,5-difluorophenyl)acetyl chloride C8H5ClF2O 详情 详情
(III) 28363 ethylene 9002-88-4 C2H4 详情 详情
(IV) 28364 5,7-difluoro-3,4-dihydro-2(1H)-naphthalenone C10H8F2O 详情 详情
(V) 28365 (2R)-5,7-difluoro-1,2,3,4-tetrahydro-2-naphthalenol C10H10F2O 详情 详情
(VI) 28366 (2R)-5,7-difluoro-1,2,3,4-tetrahydro-2-naphthalenyl methanesulfonate C11H12F2O3S 详情 详情
(VII) 28367 (2S)-2-azido-5,7-difluoro-1,2,3,4-tetrahydronaphthalene C10H9F2N3 详情 详情
(VIII) 18416 (2S)-5,7-difluoro-1,2,3,4-tetrahydro-2-naphthalenylamine; (2S)-5,7-difluoro-1,2,3,4-tetrahydro-2-naphthalenamine C10H11F2N 详情 详情
(IX) 28368 2-[[(2S)-5,7-difluoro-1,2,3,4-tetrahydro-2-naphthalenyl]amino]acetonitrile C12H12F2N2 详情 详情
(X) 28369 cyanomethyl[(2S)-5,7-difluoro-1,2,3,4-tetrahydro-2-naphthalenyl]formamide C13H12F2N2O 详情 详情
(XI) 28370 (Z)-1-cyano-2-hydroxyethenyl[(2S)-5,7-difluoro-1,2,3,4-tetrahydro-2-naphthalenyl]formamide C14H12F2N2O2 详情 详情
(XII) 28371 3-[(2S)-5,7-difluoro-1,2,3,4-tetrahydro-2-naphthalenyl]-2-thioxo-2,3-dihydro-1H-imidazole-4-carbonitrile C14H11F2N3S 详情 详情
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