2-Bromoethoxy-t-butyldimethylsilane -Drug Synthesis Database

【结构式】

【分子编号】55573

【品名】2-Bromoethoxy-t-butyldimethylsilane

【CA登记号】86864-60-0

【分子式】C₈H₁₉BrOSi

【分子量】239.22776

【元素组成】C 40.17% H 8.01% Br 33.4% O 6.69% Si 11.74%

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：(VII)

The esterification of 4-formylcinnamic acid (I) with methanol and HCl gives the methyl ester (II), which can be obtained by Heck coupling of 4-bromobenzaldehyde (III) with methyl acrylate (IV). The reductocondensation of (II) with tryptamine (V) by means of NaBH(OAc)3 in dichloroethane yields the secondary amine (VI), which is alkylated with 2-(tert-butyldimethylsilyloxy)ethyl bromide (VII) by means of DIEA in DMSO to afford the tertiary amine (VIII). The reaction of the methyl ester group of (VIII) with KOH and hydroxylamine in methanol provides the silylated hydroxamic acid (IX), which is finally deprotected with TFA in water.

参考文献中间体

合成目标

【1】 Perez, L.B.; Remiszewski, S.; Sambucetti, L.; et al.; Discovery and SAR of NVP-LAQ824, a novel histone deacetylase inhibitor with in vitro and in vivo antitumor activity. Proc Am Assoc Cancer Res 2002, 43, Abst 3671.
【2】 Bair, K.W.; Versace, R.W.; Green, M.A.; Remiszewski, S.W.; Perez, L.B.; Sambucetti, L.; Sharma, S.K. (Novartis AG; Novartis-Erfindungen VmbH); Deacetylase inhibitors. WO 0222577 .

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)	55571	4-Formylcinnamic acid	23359-08-2	C₁₀H₈O₃	详情	详情
(II)	46515	methyl (E)-3-(4-formylphenyl)-2-propenoate	7560-50-1	C₁₁H₁₀O₃	详情	详情
(III)	22231	4-Bromobenzaldehyde	1122-91-4	C₇H₅BrO	详情	详情
(IV)	14156	methyl acrylate	96-33-3	C₄H₆O₂	详情	详情
(V)	40537	Tryptamine; 2-(1H-Indol-3-yl)-1-ethanamine; 2-(1H-Indol-3-yl)ethylamine	61-54-1	C₁₀H₁₂N₂	详情	详情
(VI)	55572	methyl 3-[4-({[2-(1H-indol-3-yl)ethyl]amino}methyl)phenyl]-2-propenoate		C₂₁H₂₂N₂O₂	详情	详情
(VII)	55573	2-Bromoethoxy-t-butyldimethylsilane	86864-60-0	C₈H₁₉BrOSi	详情	详情
(VIII)	55574			C₂₉H₄₀N₂O₃Si	详情	详情
(IX)	55575	3-[4-({(2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}ethyl)[2-(1H-indol-3-yl)ethyl]amino}methyl)phenyl]-N-hydroxy-2-propenamide		C₂₈H₃₉N₃O₃Si	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IX)

Claisen condensation between 3,4-dichlorophenylacetic acid (VI) and N-Boc-sarcosine methyl ester (VII), followed by acidic decarboxylation of the intermediate keto acid, furnishes amino ketone (VIII). Alkylation of (VIII) with the silylated bromoethanol (IX) in the presence of NaH and NaI yields adduct (X). Subsequent condensation of ketone (X) with O-allyl hydroxylamine (XI) generates the corresponding oxime (XII). After desilylation of (XII) with tetrabutylammonium fluoride, the resultant primary alcohol (XIII) is oxidized under Swern conditions to furnish aldehyde (XIV)

参考文献中间体

合成目标

【1】 Carruthers, N.I.; Alaimo, C.A.; Shih, N.-Y.; Lavey, B.J.; Ting, P.C.; Reichard, G.A. (Schering Corp.); Substd. oximes as neurokinin antagonists. EP 1032561; WO 9926924 .
【2】 Carruthers, N.I.; Reichard, G.A.; Shih, N.-Y.; Lavey, B.J.; Alaimo, C.A.; Ting, P.C. (Schering Corp.); Substd. oximes as neurokinin antagonists. US 6063926 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VI)	30414	2-(3,4-dichlorophenyl)acetic acid；2-(3,4-Dichlorophenyl)acetic acid	5807-30-7	C₈H₆Cl₂O₂	详情	详情
(VII)	60815	methyl 2-[(tert-butoxycarbonyl)(methyl)amino]acetate		C₉H₁₇NO₄	详情	详情
(VIII)	60816	tert-butyl 3-(3,4-dichlorophenyl)-2-oxopropyl(methyl)carbamate		C₁₅H₁₉Cl₂NO₃	详情	详情
(IX)	55573	2-Bromoethoxy-t-butyldimethylsilane	86864-60-0	C₈H₁₉BrOSi	详情	详情
(X)	60817	tert-butyl 5-{[tert-butyl(dimethyl)silyl]oxy}-3-(3,4-dichlorophenyl)-2-oxopentyl(methyl)carbamate		C₂₃H₃₇Cl₂NO₄Si	详情	详情
(XI)	49195	3-(aminooxy)-1-propene; O-allylhydroxylamine		C₃H₇NO	详情	详情
(XII)	60818	tert-butyl 2-[(allyloxy)imino]-5-{[tert-butyl(dimethyl)silyl]oxy}-3-(3,4-dichlorophenyl)pentyl(methyl)carbamate		C₂₆H₄₂Cl₂N₂O₄Si	详情	详情
(XIII)	60819	tert-butyl 2-[(allyloxy)imino]-3-(3,4-dichlorophenyl)-5-hydroxypentyl(methyl)carbamate		C₂₀H₂₈Cl₂N₂O₄	详情	详情
(XIV)	60820	tert-butyl 2-[(allyloxy)imino]-3-(3,4-dichlorophenyl)-5-oxopentyl(methyl)carbamate		C₂₀H₂₆Cl₂N₂O₄	详情	详情

Extended Information