[4-({[tert-butyl(diphenyl)silyl]oxy}methyl)phenyl](3-pyridinyl)methanone -Drug Synthesis Database

【结构式】

【分子编号】54466

【品名】[4-({[tert-butyl(diphenyl)silyl]oxy}methyl)phenyl](3-pyridinyl)methanone

【CA登记号】

【分子式】C₂₉H₂₉NO₂Si

【分子量】451.6403

【元素组成】C 77.12% H 6.47% N 3.1% O 7.09% Si 6.22%

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：(I)

The Wittig condensation of 1-[4-(tert-butyldiphenylsilyloxymethyl)phenyl]-1-(3-pyridyl)methanone (I) with phosphonium bromide (II) by means of NaH in tert-butanol gives the heptenoic ester (III), which is desilylated with TBAF in THF to yield 7-[4-(hydroxymethyl)phenyl]-7-(3-pyridyl)-6-heptenoic acid ethyl ester (IV). The reaction of (IV) with Ms-Cl and TEA affords the corresponding mesylate (V), which is finally condensed with the triazolodiazepine (VI) by means of K2CO3 and 18-crown-6 in DMF.

参考文献中间体

合成目标

【1】 Fujita, M.; et al.; Novel agents combining platelet activating factor (PAF) receptor antagonist with thromboxane synthase inhibitor (TxSI). Bioorg Med Chem Lett 2002, 12, 5, 771.
【2】 Sano, T.; Seki, T.; Fujita, M.; Inada, H. (Nikken Chemicals Co., Ltd.); Triazolo-1,4-diazepine cpds. and medicinal compsn. containing the same. EP 0995752; JP 1999071378; US 6433167; WO 9858930 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	54466	[4-({[tert-butyl(diphenyl)silyl]oxy}methyl)phenyl](3-pyridinyl)methanone	C₂₉H₂₉NO₂Si	详情	详情
(II)	54467	(6-ethoxy-6-oxohexyl)(triphenyl)phosphonium bromide	C₂₆H₃₀BrO₂P	详情	详情
(III)	54468	ethyl (E)-7-[4-({[tert-butyl(diphenyl)silyl]oxy}methyl)phenyl]-7-(3-pyridinyl)-6-heptenoate	C₃₇H₄₃NO₃Si	详情	详情
(IV)	54469	ethyl (E)-7-[4-(hydroxymethyl)phenyl]-7-(3-pyridinyl)-6-heptenoate	C₂₁H₂₅NO₃	详情	详情
(V)	54470	ethyl (E)-7-(4-{[(methylsulfonyl)oxy]methyl}phenyl)-7-(3-pyridinyl)-6-heptenoate	C₂₂H₂₇NO₅S	详情	详情
(VI)	14057	6-(2-Chlorophenyl)-1,4-dimethyl-7,8,9,10-tetrahydro-4H-pyrido[4',3':4,5]thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine	C₁₉H₁₈ClN₅S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Treatment of 4-(t-butyldiphenylsilyloxymethyl)phenyl-(3-pyridyl)ketone (I) with hydroxylamine hydrochloride in pyridine affords oxime (II) as a mixture of geometric isomers. Then, alkylation of oxime (II) with ethyl 5-bromovalerate (III) in the presence of NaH provides ester (IV). After desilylation of (IV) with tetrabutylammonium fluoride, the deprotected primary alcohol (V) is oxidized by KMnO4 to furnish carboxylic acid (VI). Finally, DCC-mediated coupling of acid (VI) with the known tetracyclic precursor (VII) gives rise to the corresponding amide.

参考文献中间体

合成目标

【1】 Sano, T.; Seki, T.; Fujita, M.; Inada, H. (Nikken Chemicals Co., Ltd.); Triazolo-1,4-diazepine cpds. and medicinal compsn. containing the same. EP 0995752; JP 1999071378; US 6433167; WO 9858930 .

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)	54466	[4-({[tert-butyl(diphenyl)silyl]oxy}methyl)phenyl](3-pyridinyl)methanone		C₂₉H₂₉NO₂Si	详情	详情
(II)	61007	[4-({[tert-butyl(diphenyl)silyl]oxy}methyl)phenyl](3-pyridinyl)methanone oxime		C₂₉H₃₀N₂O₂Si	详情	详情
(III)	37151	ethyl 5-bromopentanoate	14660-52-7	C₇H₁₃BrO₂	详情	详情
(IV)	61008	ethyl 5-({[(E)-[4-({[tert-butyl(diphenyl)silyl]oxy}methyl)phenyl](3-pyridinyl)methylidene]amino}oxy)pentanoate		C₃₆H₄₂N₂O₄Si	详情	详情
(V)	61009	ethyl 5-({[(E)-[4-(hydroxymethyl)phenyl](3-pyridinyl)methylidene]amino}oxy)pentanoate		C₂₀H₂₄N₂O₄	详情	详情
(VI)	61010	4-[{[(5-ethoxy-5-oxopentyl)oxy]imino}(3-pyridinyl)methyl]benzoic acid		C₂₀H₂₂N₂O₅	详情	详情
(VII)	14057	6-(2-Chlorophenyl)-1,4-dimethyl-7,8,9,10-tetrahydro-4H-pyrido[4',3':4,5]thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine		C₁₉H₁₈ClN₅S	详情	详情

Extended Information