2-[(E)-2-(1-methyl-1H-indol-2-yl)ethenyl]phenol -Drug Synthesis Database

【结构式】

【分子编号】30940

【品名】2-[(E)-2-(1-methyl-1H-indol-2-yl)ethenyl]phenol

【CA登记号】

【分子式】C₁₇H₁₅NO

【分子量】249.31224

【元素组成】C 81.9% H 6.06% N 5.62% O 6.42%

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 condensation of 1-methylindole-2-carbaldehyde (I) with 2-hydroxybenzyl triphenylphosphonium bromide (II) by means of BuLi in THF gives the vinyl derivative (III), which is condensed with (R)(+)-methyl lactate (IV) by means of DEAD and PPh3 in THF yielding the chiral ether derivative (V). The reduction of the carboxylate group of (V) with DIBAL in THF affords the expected chiral propanol derivative (VI), which is cyclized with N-methylmaleimide (VII) by heating at 180 C and aromatized with DDQ giving the pyrrolocarbazole (VIII). The reaction of the hydroxy group of (VIII) with tosyl chloride and pyridine yields the corresponding tosylate (IX), which is finally condensed with dimethylamine in hot DMF.

参考文献中间体

合成目标

【1】 Ikuina, Y.; et al.; Synthesis and structure-activity relationships of pyrrolocarbazole derivatives possessing thrombopoietic activity. 217th ACS Natl Meet (March 21 1999, Anaheim) 1999, Abst MEDI 089.
【2】 Ikuina, Y.; Murakata, C.; Saitoh, Y.; Shiotsu, Y.; Iida, T.; Tamaoki, T.; Yamashita, K.; Akinaga, S. (Kyowa Hakko Kogyo Co., Ltd.); Pyrrolocarbazole derivs.. EP 0768311; US 5728709; WO 9628447 .

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)	30938	1-methyl-1H-indole-2-carbaldehyde		C₁₀H₉NO	详情	详情
(II)	30939	(2-hydroxybenzyl)(triphenyl)phosphonium bromide	70340-04-4	C₂₅H₂₂BrOP	详情	详情
(III)	30940	2-[(E)-2-(1-methyl-1H-indol-2-yl)ethenyl]phenol		C₁₇H₁₅NO	详情	详情
(IV)	11591	methyl (2R)-2-hydroxypropanoate	17392-83-5	C₄H₈O₃	详情	详情
(V)	30941	methyl (2S)-2-[2-[(E)-2-(1-methyl-1H-indol-2-yl)ethenyl]phenoxy]propanoate		C₂₁H₂₁NO₃	详情	详情
(VI)	30942	(2S)-2-[2-[(E)-2-(1-methyl-1H-indol-2-yl)ethenyl]phenoxy]-1-propanol		C₂₀H₂₁NO₂	详情	详情
(VII)	30943	1-methyl-1H-pyrrole-2,5-dione	930-88-1	C₅H₅NO₂	详情	详情
(VIII)	30944	4-(2-[[(1S)-2-hydroxy-1-methylethyl]oxy]phenyl)-2,6-dimethylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione		C₂₅H₂₂N₂O₄	详情	详情
(IX)	30945	(2S)-2-[2-(2,6-dimethyl-1,3-dioxo-1,2,3,6-tetrahydropyrrolo[3,4-c]carbazol-4-yl)phenoxy]propyl 4-methylbenzenesulfonate		C₃₂H₂₈N₂O₆S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

The condensation of 1-methylindole-2-carbaldehyde (I) with 2-hydroxybenzyl triphenylphosphonium bromide (II) by means of BuLi in THF gives the vinyl derivative (III), which is condensed with (rac)-methyl lactate (IV) by means of DEAD and PPh3 in THF yielding the ether derivative (V). The reduction of the carboxylate group of (V) with DIBAL in THF affords the expected propanol derivative (VI), which is cyclized with N-methylmaleimide (VII) by heating at 180 C and aromatized with DDQ giving the pyrrolocarbazole (VIII). The reaction of the hydroxy group of (VIII) with tosyl chloride and pyridine yields the corresponding tosylate (IX), which is finally condensed with dimethylamine in hot DMF.

参考文献中间体

合成目标

【1】 Ikuina, Y.; et al.; Synthesis and structure-activity relationships of pyrrolocarbazole derivatives possessing thrombopoietic activity. 217th ACS Natl Meet (March 21 1999, Anaheim) 1999, Abst MEDI 089.
【2】 Ikuina, Y.; Murakata, C.; Saitoh, Y.; Shiotsu, Y.; Iida, T.; Tamaoki, T.; Yamashita, K.; Akinaga, S. (Kyowa Hakko Kogyo Co., Ltd.); Pyrrolocarbazole derivs.. EP 0768311; US 5728709; WO 9628447 .

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)	30938	1-methyl-1H-indole-2-carbaldehyde		C₁₀H₉NO	详情	详情
(II)	30939	(2-hydroxybenzyl)(triphenyl)phosphonium bromide	70340-04-4	C₂₅H₂₂BrOP	详情	详情
(III)	30940	2-[(E)-2-(1-methyl-1H-indol-2-yl)ethenyl]phenol		C₁₇H₁₅NO	详情	详情
(IV)	30946	methyl 2-hydroxypropanoate		C₄H₈O₃	详情	详情
(V)	30947	methyl 2-[2-[(E)-2-(1-methyl-1H-indol-2-yl)ethenyl]phenoxy]propanoate		C₂₁H₂₁NO₃	详情	详情
(VI)	30948	2-[2-[(E)-2-(1-methyl-1H-indol-2-yl)ethenyl]phenoxy]-1-propanol		C₂₀H₂₁NO₂	详情	详情
(VII)	30943	1-methyl-1H-pyrrole-2,5-dione	930-88-1	C₅H₅NO₂	详情	详情
(VIII)	30949	4-[2-(2-hydroxy-1-methylethoxy)phenyl]-2,6-dimethylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione		C₂₅H₂₂N₂O₄	详情	详情
(IX)	30950	2-[2-(2,6-dimethyl-1,3-dioxo-1,2,3,6-tetrahydropyrrolo[3,4-c]carbazol-4-yl)phenoxy]propyl 4-methylbenzenesulfonate		C₃₂H₂₈N₂O₆S	详情	详情

Extended Information