D-64131, -Drug Synthesis Database

【结构式】

【药物名称】D-64131

【化学名称】1-(5-Methoxy-1H-indol-2-yl)-1-phenylmethanone

【CA登记号】74588-78-6

【分子式】C₁₆H₁₃NO₂

【分子量】251.28751

【开发单位】Baxter Oncology (Originator)

【药理作用】ONCOLYTIC DRUGS, Antimitotic Drugs, Microtubule-Stabilizing Agents

合成路线1 合成路线2 合成路线3

合成路线1

Protection of 5-methoxyindole (I) with benzenesulfonyl chloride (II) in the presence of NaH affords the N-sulfonyl indole (III). Acylation of the 2-lithio derivative of (III) with benzoyl chloride (IV) gives rise to ketone (V). Finally, removal of the phenylsulfonyl protecting group of (V) is achieved by either basic hydrolysis or by treatment with tetrabutylammonium fluoride.

参考文献中间体

【1】 Hufsky, H.; Pongratz, H.; Mahboobi, S.; et al.; Synthetic 2-aroylindole derivatives as a new class of potent tubulin-inhibitory, antimitotic agents. J Med Chem 2001, 44, 26, 4535.
【2】 Teller, S.; Pongratz, H.; Mahboobi, S.; et al.; Bis(1H-2-indolyl) methanones as a novel class of inhibitors of the platelet-derived growth factor receptor kinase. J Med Chem 2002, 45, 5, 1002.
【3】 Burger, A.; Mahboobi, S.; Pongratz, H.; Hufsky, H.; Böhmer, F.-D.; Beckers, T.; Klenner, T.; Baasner, S.; Frieser, M.; Hockemeyer, J.; Fiebig, H.-H. (Asta Medica AG); 2-Acyl indol derivs. and their use as anti-tumour agents. DE 10020852; WO 0182909 .

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)	25902	1H-Indol-5-yl methyl ether; 5-Methoxy-1H-indole; 5-Methoxyindole	1006-94-6	C₉H₉NO	详情	详情
(II)	14713	benzenesulfonyl chloride	98-09-9	C₆H₅ClO₂S	详情	详情
(III)	57928	5-methoxy-1-(phenylsulfonyl)-1H-indole; methyl 1-(phenylsulfonyl)-1H-indol-5-yl ether		C₁₅H₁₃NO₃S	详情	详情
(IV)	10463	Benzoyl chloride	98-88-4	C₇H₅ClO	详情	详情
(V)	57929	[5-methoxy-1-(phenylsulfonyl)-1H-indol-2-yl](phenyl)methanone		C₂₂H₁₇NO₄S	详情	详情

合成路线2

In a related method, the 2-lithio derivative of 5-methoxy-1-(phenylsulfonyl)indole (I) is condensed with benzaldehyde (II) to produce carbinol (III). Subsequent oxidation of (III) to the corresponding ketone (IV) is accomplished by treatment with pyridinium dichromate (PDC) in the presence of pyridinium trifluoroacetate (PTFA). Finally, the N-phenylsulfonyl group of (IV) is deprotected by treatment with tetrabutylammonium fluoride.

参考文献中间体

【1】 Teller, S.; Pongratz, H.; Mahboobi, S.; et al.; Bis(1H-2-indolyl) methanones as a novel class of inhibitors of the platelet-derived growth factor receptor kinase. J Med Chem 2002, 45, 5, 1002.

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)	57928	5-methoxy-1-(phenylsulfonyl)-1H-indole; methyl 1-(phenylsulfonyl)-1H-indol-5-yl ether		C₁₅H₁₃NO₃S	详情	详情
(II)	10498	Benzaldehyde;Benzoic aldehyde;Phenylmethanal	100-52-7	C₇H₆O	详情	详情
(III)	57930	[5-methoxy-1-(phenylsulfonyl)-1H-indol-2-yl](phenyl)methanol		C₂₂H₁₉NO₄S	详情	详情
(IV)	57929	[5-methoxy-1-(phenylsulfonyl)-1H-indol-2-yl](phenyl)methanone		C₂₂H₁₇NO₄S	详情	详情

合成路线3

The alkaline hydrolysis of 5-methoxyisatin (I) provides the ortho-(aminophenyl)glyoxylic acid salt (II), which is then alkylated by 2-bromoacetophenone (III) to furnish the N-phenacylisatin (IV). Rearrangement of (IV) in the presence of NaOH gives rise to a 40:60 mixture of the indolecarboxylic acid (V) and the target decarboxylated compound.

参考文献中间体

【1】 Black, D.S.C.; Wong, L.C.H.; A simple synthesis of 2-acyl indoles from isatins. J Chem Soc Chem Commun 1980, 4, 200.

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)	11892	5-Methoxy-1H-indole-2,3-dione	39755-95-8	C₉H₇NO₃	详情	详情
(II)	57931	sodium 2-(2-amino-5-methoxyphenyl)-2-oxoacetate		C₉H₈NNaO₄	详情	详情
(III)	10315	2-Bromo-1-phenyl-ethanone; 2-Bromo-1-phenyl-1-ethanone	70-11-1	C₈H₇BrO	详情	详情
(IV)	57932	5-methoxy-1-(2-oxo-2-phenylethyl)-1H-indole-2,3-dione		C₁₇H₁₃NO₄	详情	详情
(V)	57933	2-benzoyl-5-methoxy-1H-indole-3-carboxylic acid		C₁₇H₁₃NO₄	详情	详情

Extended Information