1-(2,5-dihydroxyphenyl)-1-ethanone -Drug Synthesis Database

【结构式】

【分子编号】38479

【品名】1-(2,5-dihydroxyphenyl)-1-ethanone

【CA登记号】490-78-8

【分子式】C₈H₈O₃

【分子量】152.14972

【元素组成】C 63.15% H 5.3% O 31.55%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(I)

Chromanone (II) was prepared by reaction of 2',5'-dihydroxyacetophenone (I) with acetone and pyrrolidine. Alkylation of the hydroxyl group of (II) with 4,4,4-trifluorobutyl bromide in the presence of NaH provided ether (III). The keto group of (III) was then reduced to alcohol (IV), which was subsequently dehydrated to chomene (V) by means of p-toluenesulfonic acid in hot toluene. Asymmetric epoxidation of (V) with NaOCl employing the chiral auxiliary (R,R)-bis(3,5-di-tert-butylsalicylidene)-1,2-diaminocyclohexane manganese (III) chloride furnished epoxide (VI). Finally, epoxide opening by the sodium salt of N-methyl methanesulfonamide afforded the title compound.

参考文献中间体

合成目标

【1】 Lang, H.J.; Gerlach, U.; Weldmann, K.; Brendel, J. (Aventis Pharma Deutschland GmbH); Sulphonamide substd. benzopyran derivs., process of preparation, their use as medicines and pharmaceutical compsns. containing them. CA 2252733; DE 19748469; EP 0913396; JP 1999222485; US 6008245 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	40431	2-[(6aR,9S,10aR)-7-methyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinolin-9-yl]acetonitrile		C₁₇H₁₉N₃	详情	详情
	40730	1-Bromo-4,4,4-trifluorobutane 1-Bromo-4,4,4-trifluorobutane	406-81-5	C₄H₆BrF₃	详情	详情
(I)	38479	1-(2,5-dihydroxyphenyl)-1-ethanone	490-78-8	C₈H₈O₃	详情	详情
(II)	38480	6-hydroxy-2,2-dimethyl-2,3-dihydro-4H-chromen-4-one		C₁₁H₁₂O₃	详情	详情
(III)	38481	2,2-dimethyl-6-(4,4,4-trifluorobutoxy)-2,3-dihydro-4H-chromen-4-one		C₁₅H₁₇F₃O₃	详情	详情
(IV)	38482	2,2-dimethyl-6-(4,4,4-trifluorobutoxy)-4-chromanol		C₁₅H₁₉F₃O₃	详情	详情
(V)	38483	2,2-dimethyl-6-(4,4,4-trifluorobutoxy)-2H-chromene; 2,2-dimethyl-2H-chromen-6-yl 4,4,4-trifluorobutyl ether		C₁₅H₁₇F₃O₂	详情	详情
(VI)	38484	(1aR,7bR)-2,2-dimethyl-1a,7b-dihydro-2H-oxireno[2,3-c]chromen-6-yl 4,4,4-trifluorobutyl ether; (1aR,7bR)-2,2-dimethyl-6-(4,4,4-trifluorobutoxy)-1a,7b-dihydro-2H-oxireno[2,3-c]chromene		C₁₅H₁₇F₃O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Reaction of 2',5'-dihydroxyacetophenone (I) with dihydropyran (II) and pyridinium p-toluenesulfonate gives the protected bis-tetrahydropyranyl ether (III), which is submitted to Claisen-Schmidt condensation with 2-chlorobenzaldehyde (IV) in the presence of barium hydroxide, yielding the chalcone (V). Finally, the tetrahydropyranyl protecting groups of (V) are removed by acidic hydrolysis with p-toluenesulfonic acid in MeOH.

参考文献中间体

合成目标

【1】 Nam, N.-H.; Kim, Y.; You, Y.-J.; Hong, D.-H.; Kim, H.-M.; Ahn, B.-Z.; Cytotoxic 2',5'-dihydroxychalcones with unexpected antiangiogenic activity. Eur J Med Chem 2003, 38, 2, 179.

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)	38479	1-(2,5-dihydroxyphenyl)-1-ethanone	490-78-8	C₈H₈O₃	详情	详情
(II)	13684	3,4-Dihydro-2H-pyran;2,3-Dihydro-4H-pyran; 5,6-Dihydro-4H-pyran;Dihydropyran	110-87-2	C₅H₈O	详情	详情
(III)	64828	1-[2,5-bis(tetrahydro-2H-pyran-2-yloxy)phenyl]-1-ethanone		C₁₈H₂₄O₅	详情	详情
(IV)	24114	2-chlorobenzaldehyde	89-98-5	C₇H₅ClO	详情	详情
(V)	64829	(E)-1-[2,5-bis(tetrahydro-2H-pyran-2-yloxy)phenyl]-3-(2-chlorophenyl)-2-propen-1-one		C₂₅H₂₇ClO₅	详情	详情

合成路线3

该中间体在本合成路线中的序号：(XI)

Selective O-protection of 2,5-dihydroxyacetophenone (XI) with benzyl bromide by means of K2Co3 in acetone or methylisobutylketone yields 2’-hydroxy-5’-benzyloxyacetophenone (XII) , which is then nitrated with fuming Hno3 in AcoH to give the 3’-nitroacetophenone derivative (XIII) . Reduction of the nitro group in compound (XIII) by catalytic hydrogenation over Rh/C in MeoH or Pto2 in 2-MeTHF (4, 5) provides the corresponding aniline (XIV) , which finally undergoes cyclization with chloroacetyl chloride (XV) in the presence of K2Co3 in refluxing acetonitrile or 2-MeTHF .

参考文献中间体

合成目标

【1】 Bouyssou, T., Hoenke, C., Rudolf, K. et al. Discovery of olodaterol, a novel inhaled b2-adrenoceptor agonist with a 24 h bronchodilatory efficacy. Bioorg Med Chem Lett 2010, 20(4): 1410-4.
【2】 Konetzki, I., Lustenberger, P., Sieger, P. (Boehringer Ingelheim Pharma GmbH & Co. KG). Novel enantiomerically pure beta-agonists, method for the production and the use thereof in the form of a drug. EP 1789405, JP 2007537196, US 2005267106, US 2007027148, US 7220742, US 7491719, US 2009137578, US 8034809, Wo 2005111005.
【3】 Krueger, T., Ries, U., Schnaubelt, J., Rall, W., Leuter, Z.A., Duran, A., Soyka, R. (Boehringer Ingelheim Pharma GmbH & Co. KG). Method for producing betamimetics. EP 1917253, JP 2009504708, US 201114859, Wo 2007020227.
【4】 Rodriguez Dehli, J.M., Hagenkoetter, R., Schul, M., Stange, C. (Boehringer Ingelheim Pharma GmbH & Co. KG). Method for producing betamimetics. EP 2125759, JP 2010516739, US 2010022770, Wo 2008090193.

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)	68012	8-acetyl-6-benzyloxy-1,4-benzoxazin-3-one		C₁₇H₁₅NO₄	详情	详情
(XI)	38479	1-(2,5-dihydroxyphenyl)-1-ethanone	490-78-8	C₈H₈O₃	详情	详情
(XII)	20133	1-[5-(benzyloxy)-2-hydroxyphenyl]-1-ethanone		C₁₅H₁₄O₃	详情	详情
(XIII)	68024	1-(5-(benzyloxy)-2-hydroxy-3-nitrophenyl)ethanone		C₁₅H₁₃NO₅	详情	详情
(XIV)	68025	1-(3-amino-5-(benzyloxy)-2-hydroxyphenyl)ethanone		C₁₅H₁₅NO₃	详情	详情
(XV)	11296	2-Chloroacetyl chloride; Chloroacetic chloride	79-04-9	C₂H₂Cl₂O	详情	详情

Extended Information