(E)-3-(3,4-dimethoxyphenyl)-1-(3-hydroxyphenyl)-2-propen-1-one -Drug Synthesis Database

【结构式】

【分子编号】25332

【品名】(E)-3-(3,4-dimethoxyphenyl)-1-(3-hydroxyphenyl)-2-propen-1-one

【CA登记号】

【分子式】C₁₇H₁₆O₄

【分子量】284.31164

【元素组成】C 71.82% H 5.67% O 22.51%

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：(III)

The intermediate alcohol (VIII) was prepared as shown in Scheme 27060901a: Aldol condensation of 3,4-dimethoxybenzaldehyde (I) with 3-hydroxyacetophenone (II) in the presence of KOH provided chalcone (III), which was hydrogenated over Pd/C to yield the corresponding diarylpropanone (IV). Subsequent alkylation of the phenolic hydroxyl group of (IV) with tert-butyl bromoacetate (V) using NaH in DMF gave ether (VI). Then, enantioselective reduction of ketone by means of (+)-beta-chlorodiisopinocampheylborane (VII) at -20 C furnished the (R)-alcohol (VIII).

参考文献中间体

合成目标

【1】 Yang, W.; Guo, T.; Keenan, T.P.; Laborde, E.; Holt, D.A. (Ariad Pharmaceuticals Inc.); Synthetic derivs. of rapamycin as multimerizing agents for chimeric proteins with immunophilin-derived domains. JP 2000505475; WO 9731898 .

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)	18304	3,4-Dimethoxybenzaldehyde; Veratraldehyde	120-14-9	C₉H₁₀O₃	详情	详情
(II)	25331	3-hydroxyacetophenone; 1-(3-hydroxyphenyl)-1-ethanone	121-71-1	C₈H₈O₂	详情	详情
(III)	25332	(E)-3-(3,4-dimethoxyphenyl)-1-(3-hydroxyphenyl)-2-propen-1-one		C₁₇H₁₆O₄	详情	详情
(IV)	25341	3-(3,4-dimethoxyphenyl)-1-(3-hydroxyphenyl)-1-propanone		C₁₇H₁₈O₄	详情	详情
(V)	17430	2-Bromoacetic acid tert-butyl ester; tert-butyl 2-bromoacetate; tert-Butyl bromoacetate	5292-43-3	C₆H₁₁BrO₂	详情	详情
(VI)	25342	tert-butyl 2-[3-[3-(3,4-dimethoxyphenyl)propanoyl]phenoxy]acetate		C₂₃H₂₈O₆	详情	详情
(VII)	25343	chloro[bis[(1S,2R,3S,5S)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]]borane	112246-73-8	C₂₀H₃₄BCl	详情	详情
(VIII)	25348	tert-butyl 2-[3-[(1R)-3-(3,4-dimethoxyphenyl)-1-hydroxypropyl]phenoxy]acetate		C₂₃H₃₀O₆	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

Selective protection of the 7-hydroxyl group of deacetylbaccatin (I) with triethylsilyl chloride provided silyl ether (II), which was acetylated at position 10 using acetyl chloride and lithium hexamethyldisilazide. Further coupling of (II) with beta-lactam (III) gave (IV), which by selective removal of the 7-silyl group with 0.1 N HCl gave 10-acetyl-2'-(triisopropylsilyl)docetaxel (V). This was condensed with benzoylcinnamic acid (VI) employing EDC and DMAP to afford ester (VII).

参考文献中间体

合成目标

【1】 Ahern, D.G.; Ojima, I.; Bounaud, P.-Y.; New photoaffinity analogs of paclitaxel. Bioorg Med Chem Lett 1999, 9, 8, 1189.

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)	25331	3-hydroxyacetophenone; 1-(3-hydroxyphenyl)-1-ethanone	121-71-1	C₈H₈O₂	详情	详情
(II)	25332	(E)-3-(3,4-dimethoxyphenyl)-1-(3-hydroxyphenyl)-2-propen-1-one		C₁₇H₁₆O₄	详情	详情
(III)	25333	tert-butyl (3R,4S)-2-oxo-4-phenyl-3-[(triisopropylsilyl)oxy]-1-azetidinecarboxylate		C₂₃H₃₇NO₄Si	详情	详情
(IV)	25334	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-([(2R,3S)-3-[(tert-butoxycarbonyl)amino]-3-phenyl-2-[(triisopropylsilyl)oxy]propanoyl]oxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]h		C₆₀H₈₉NO₁₅Si₂	详情	详情
(V)	25335	(1S,2S,3R,4S,7R,9S,10R,12R,15S)-4,12-bis(acetoxy)-15-([(2R,3S)-3-[(tert-butoxycarbonyl)amino]-3-phenyl-2-[(triisopropylsilyl)oxy]propanoyl]oxy)-1,9-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl		C₅₄H₇₅NO₁₅Si	详情	详情
(VI)	25336	(E)-3-(3-benzoylphenyl)-2-propenoic acid		C₁₆H₁₂O₃	详情	详情
(VII)	25337	(1S,2S,3R,4S,7R,9S,10R,12R,15S)-4,12-bis(acetoxy)-9-[[(E)-3-(3-benzoylphenyl)-2-propenoyl]oxy]-15-([(2R,3S)-3-[(tert-butoxycarbonyl)amino]-3-phenyl-2-[(triisopropylsilyl)oxy]propanoyl]oxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[1		C₇₀H₈₅NO₁₇Si	详情	详情

Extended Information