N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide -Drug Synthesis Database

【结构式】

【分子编号】55550

【品名】N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide

【CA登记号】

【分子式】C₁₇H₁₈N₂O₅S

【分子量】362.4064

【元素组成】C 56.34% H 5.01% N 7.73% O 22.07% S 8.85%

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：(VII)

The reaction of indoline (I) with formic acid in refluxing toluene gives N-formylindoline (II), which is treated with chlorosulfonic acid to yield 5-(chlorosulfonyl)indoline-1-carbaldehyde (III). The reaction of (III) with 3,4,5-trimethoxyaniline (IV) and pyridine in THF affords the sulfonamide (V), which is deformylated to sulfonamide (VI) with HCl in methanol. The reaction of indoline (VI) with salcomine and O2 in methanol provides the corresponding indole derivative (VII), which is finally methylated with methyl iodide and NaHMDS in THF to give the target 1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide.

参考文献中间体

合成目标

【2】 Barr, K.J.; Steiner, B.A.; Qun, L.; Rosenberg, S.; Sham, H.; Gwaltney, S.L. II; Imade, H.M.; Woods, K.W. (Abbott Laboratories Inc.); Cell proliferation inhibitors. WO 0073264 .
【1】 Li, Q.; Woods, K.W.; Steiner, A.; et al.; Synthesis and biological evaluation of biarylsulfonamides as tubulin polymerization inhibitors. Discovery of A-318315 and A-293620 as orally and intravenously active antimitotic agents. Proc Am Assoc Cancer Res 2002, 43, Abst 1313.

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)	19652	indoline	496-15-1	C₈H₉N	详情	详情
(II)	55546	1-Formylindoline	2861-59-8	C₉H₉NO	详情	详情
(III)	55547	1-formyl-5-indolinesulfonyl chloride		C₉H₈ClNO₃S	详情	详情
(IV)	31545	3,4,5-trimethoxyaniline; 3,4,5-trimethoxyphenylamine；3,4,5-Trimethoxybenzenamine；[3,4,5-Tris(methyloxy)phenyl]amine	24313-88-0	C₉H₁₃NO₃	详情	详情
(V)	55548	1-formyl-N-(3,4,5-trimethoxyphenyl)-5-indolinesulfonamide		C₁₈H₂₀N₂O₆S	详情	详情
(VI)	55549	N-(3,4,5-trimethoxyphenyl)-5-indolinesulfonamide		C₁₇H₂₀N₂O₅S	详情	详情
(VII)	55550	N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide		C₁₇H₁₈N₂O₅S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VII)

The reaction of indoline (I) with formic acid in refluxing toluene gives N-formylindoline (II), which is treated with chlorosulfonic acid to yield 5-(chlorosulfonyl)indoline-1-carbaldehyde (III). The reaction of (III) with 3,4,5-trimethoxyaniline (IV) and pyridine in THF affords the sulfonamide (V), which is deformylated to sulfonamide (VI) with HCl in methanol. The reaction of indoline (VI) with salcomine and O2 in methanol provides the corresponding indole derivative (VII), which is methylated with methyl iodide and NaHMDS in THF to give 1-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide (VIII). Finally, this compound is condensed with N,N-dimethylglycine (IX) by means of DCC and 4-(1-pyrrolidinyl)pyridine (pypyr) in dichloromethane.

参考文献中间体

合成目标

【1】 Li, Q.; Woods, K.W.; Steiner, A.; et al.; Synthesis and biological evaluation of biarylsulfonamides as tubulin polymerization inhibitors. Discovery of A-318315 and A-293620 as orally and intravenously active antimitotic agents. Proc Am Assoc Cancer Res 2002, 43, Abst 1313.
【2】 Barr, K.J.; Steiner, B.A.; Qun, L.; Rosenberg, S.; Sham, H.; Gwaltney, S.L. II; Imade, H.M.; Woods, K.W. (Abbott Laboratories Inc.); Cell proliferation inhibitors. WO 0073264 .

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)	19652	indoline	496-15-1	C₈H₉N	详情	详情
(II)	55546	1-Formylindoline	2861-59-8	C₉H₉NO	详情	详情
(III)	55547	1-formyl-5-indolinesulfonyl chloride		C₉H₈ClNO₃S	详情	详情
(IV)	31545	3,4,5-trimethoxyaniline; 3,4,5-trimethoxyphenylamine；3,4,5-Trimethoxybenzenamine；[3,4,5-Tris(methyloxy)phenyl]amine	24313-88-0	C₉H₁₃NO₃	详情	详情
(V)	55548	1-formyl-N-(3,4,5-trimethoxyphenyl)-5-indolinesulfonamide		C₁₈H₂₀N₂O₆S	详情	详情
(VI)	55549	N-(3,4,5-trimethoxyphenyl)-5-indolinesulfonamide		C₁₇H₂₀N₂O₅S	详情	详情
(VII)	55550	N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamide		C₁₇H₁₈N₂O₅S	详情	详情
(VIII)	55569	1-methyl-N-[3,4,5-tris(methyloxy)phenyl]-1H-indole-5-sulfonamide		C₁₈H₂₀N₂O₅S	详情	详情
(IX)	16765	2-(dimethylamino)acetic acid; N,N-Dimethylglycine	1118-68-9	C₄H₉NO₂	详情	详情

Extended Information