[(4-methylphenyl)sulfonyl](3,4,5-trimethoxyphenyl)methylformamide -Drug Synthesis Database

【结构式】

【分子编号】49071

【品名】[(4-methylphenyl)sulfonyl](3,4,5-trimethoxyphenyl)methylformamide

【CA登记号】

【分子式】C₁₈H₂₁NO₆S

【分子量】379.43388

【元素组成】C 56.98% H 5.58% N 3.69% O 25.3% S 8.45%

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 between 3,4,5-trimethoxybenzaldehyde (I), 4-methylbenzenesulfinic acid (II) and formamide in the presence of camphorsulfonic acid gave tosyl-(3,4,5-trimethoxyphenyl)methylformamide (III), which was subsequently dehydrated to the isonitrile (IV) by treatment with POCl3 and Et3N. After conversion of 4-methoxy-3-nitrobenzaldehyde (V) to the corresponding imine with methylamine, its reaction with the tosylmethyl isonitrile (IV) gave rise to the diaryl imidazole (VI). The nitro group of (VI) was finally reduced to amine by using SnCl2 and HCl or ammonium formiate and Pd/C

参考文献中间体

合成目标

【1】 Wang, L.; Woods, K.W.; Li, Q.; Barr, K.J.; McCroskey, R.M.; Hannick, S.M.; Gherke, L.; Credo, R.B.; Hui, Y.H.; Marsch, K.; Warner, R.; Lee, J.Y.; Zielinski-Mozng, N.; Frost, D.; Rosenberg, S.H.; Sham, H.L.; Potent, orally active heterocycle-based combretastatin A-4 analogues: Synthesis, structure-activity relationship, pharmacokinetics, and in vivo antitumor activity evaluation. J Med Chem 2002, 45, 8, 1697.
【2】 Wang, L.; Woods, K.W.; Li, Q.; Sham, H.L. (Abbott Laboratories Inc.); Imidazole antiproliferative agents. WO 0109103 .

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)	11136	3,4,5-Trimethoxybenzaldehyde	86-81-7	C₁₀H₁₂O₄	详情	详情
(II)	25593	4-methylbenzenesulfinic acid		C₇H₈O₂S	详情	详情
(III)	49071	[(4-methylphenyl)sulfonyl](3,4,5-trimethoxyphenyl)methylformamide		C₁₈H₂₁NO₆S	详情	详情
(IV)	49072	2-[(4-methylphenyl)sulfonyl]-2-(3,4,5-trimethoxyphenyl)acetonitrile		C₁₈H₁₉NO₅S	详情	详情
(V)	18225	4-METHOXY-3-NITROBENZALDEHYDE	31680-08-7	C₈H₇NO₄	详情	详情
(VI)	49073	2,3-dimethoxy-5-[5-(4-methoxy-3-nitrophenyl)-1-methyl-1H-imidazol-4-yl]phenyl methyl ether; 5-(4-methoxy-3-nitrophenyl)-1-methyl-4-(3,4,5-trimethoxyphenyl)-1H-imidazole		C₂₀H₂₁N₃O₆	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 3,4,5-trimethoxybenzaldehyde (I) with 4-methylphenylsulfinic acid (II) and formamide by means of hot CSA gives the adduct (III), which is treated with POCl3 in DME to yield the isonitrile (IV). The reaction of benzaldehyde (V) with methylamine and AcOH in refluxing ethanol gives the enamine (VI), which is finally cyclized with isonitrile (IV) by means of K2CO3 in ethanol/DME to afford the target 1-methylimidazole.

参考文献中间体

合成目标

【1】 Wang, L.; Woods, K.W.; Li, Q.; Barr, K.J.; McCroskey, R.M.; Hannick, S.M.; Gherke, L.; Credo, R.B.; Hui, Y.H.; Marsch, K.; Warner, R.; Lee, J.Y.; Zielinski-Mozng, N.; Frost, D.; Rosenberg, S.H.; Sham, H.L.; Potent, orally active heterocycle-based combretastatin A-4 analogues: Synthesis, structure-activity relationship, pharmacokinetics, and in vivo antitumor activity evaluation. J Med Chem 2002, 45, 8, 1697.

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)	11136	3,4,5-Trimethoxybenzaldehyde	86-81-7	C₁₀H₁₂O₄	详情	详情
(II)	25593	4-methylbenzenesulfinic acid		C₇H₈O₂S	详情	详情
(III)	49071	[(4-methylphenyl)sulfonyl](3,4,5-trimethoxyphenyl)methylformamide		C₁₈H₂₁NO₆S	详情	详情
(IV)	49072	2-[(4-methylphenyl)sulfonyl]-2-(3,4,5-trimethoxyphenyl)acetonitrile		C₁₈H₁₉NO₅S	详情	详情
(V)	63173	3,4-bis[(E)-2-(methylamino)ethenyl]benzaldehyde		C₁₃H₁₆N₂O	详情	详情
(VI)	63174	(E)-N-methyl-2-{2-[(E)-2-(methylamino)ethenyl]-4-[(methylamino)methyl]phenyl}-1-ethenamine; N-{3,4-bis[(E)-2-(methylamino)ethenyl]benzyl}-N-methylamine		C₁₄H₂₁N₃	详情	详情

Extended Information