3-(3,4-dimethoxyphenyl)-1-(3-hydroxyphenyl)-1-propanone -Drug Synthesis Database

【结构式】

【分子编号】25341

【品名】3-(3,4-dimethoxyphenyl)-1-(3-hydroxyphenyl)-1-propanone

【CA登记号】

【分子式】C₁₇H₁₈O₄

【分子量】286.32752

【元素组成】C 71.31% H 6.34% O 22.35%

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：(IV)

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 acylated at position 10 with the activated ester (III) in the presence of lithium hexamethyldisilazide to give the benzoylcinnamic ester (IV). Further coupling of (IV) with beta-lactam (V) gave (VI), which by removal of the silyl groups with HF in pyridine-acetonitrile afforded (VII). The Boc group of (VII) was then removed with trifluoroacetic acid to give amine (VIII).

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)	25341	3-(3,4-dimethoxyphenyl)-1-(3-hydroxyphenyl)-1-propanone		C₁₇H₁₈O₄	详情	详情
(III)	25344	2-[[(E)-3-(3-benzoylphenyl)-2-propenoyl]oxy]-1H-isoindole-1,3(2H)-dione		C₂₄H₁₅NO₅	详情	详情
(IV)	25345	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-12-[[(E)-3-(3-benzoylphenyl)-2-propenoyl]oxy]-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate		C₅₁H₆₀O₁₂Si	详情	详情
(V)	25333	tert-butyl (3R,4S)-2-oxo-4-phenyl-3-[(triisopropylsilyl)oxy]-1-azetidinecarboxylate		C₂₃H₃₇NO₄Si	详情	详情
(VI)	25346	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-12-[[(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-9-[(triethylsilyl)oxy]		C₇₄H₉₇NO₁₆Si₂	详情	详情
(VII)	25347	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-12-[[(E)-3-(3-benzoylphenyl)-2-propenoyl]oxy]-15-([(2R,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-3-phenylpropanoyl]oxy)-1,9-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,		C₅₉H₆₃NO₁₆	详情	详情
(VIII)	25382	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-15-[[(2R,3S)-3-amino-2-hydroxy-3-phenylpropanoyl]oxy]-12-[[(E)-3-(3-benzoylphenyl)-2-propenoyl]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		C₅₄H₅₅NO₁₄	详情	详情

Extended Information