• English
  • 简体中文
Login Register
Current Location: Home > Feedback Help Print

【结 构 式】

【分子编号】12628

【品名】4-(Benzyloxy)-5-methoxy-1-methyl-1H-indole-2-carbaldehyde

【CA登记号】

【 分 子 式 】C18H17NO3

【 分 子 量 】295.33792

【元素组成】C 73.2% H 5.8% N 4.74% O 16.25%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(XXXII)

2) The esterification of 2-hydroxy-3-methoxybenzaldehyde (XXIV) with methanesulfonyl chloride and triethylamine gives the corresponding mesylate (XXV), which is nitrated with fuming HNO3 to 2-(methanesulfonyloxy)-3-methoxy-6-nitrobenzaldehyde (XXVI). The condensation of (XXVI) or 2-(benzenesulfonyloxy)-3-methoxy-6-nitrobenzaldehyde (XXVIII) with 2-(diethoxyphosphoryl)acetic acid methyl ester by means of NaH in THF yields 3-(2-hydroxy-3-methoxy-6-nitrophenyl)acrylic acid methyl ester (XXVII), which is benzylated with benzyl bromide and K2CO3 to the benzyl derivative (XXIX). The cyclization of (XXIX) with refluxing triethyl phosphite affords 4-benzyloxy-5-methoxy-1H-indole-2-carboxylic acid methyl ester (XXX), which is reduced to the corresponding carbaldehyde (XXXI) according to Tetrahedron Lett 1994, 50: 7657. The methylation of (XXXI) with NaH and methyl iodide in DMF yields the N-methyl derivative (XXXII), which is condensed with 2-(diethoxyphosphoryl)acetic acid methyl ester by means of NaH in THF to afford 3-(4-benzyloxy-5-methoxy-1-methylindol-2-yl)acrylic acid methyl ester (XXXIII). The formylation of (XXXIII) with POCl3 and DMF gives the 4-formyl derivative (XXXIV), which is debenzylated with trimethylsilyl iodide in acetonitrile to the 4-hydroxy compound (XXXV). The oxidation of (XXXV) with Fremy's salt as before yields 3-(3-formyl-5-methoxy-1-methyl-4,7-dioxo-4,7-dihydro-1H-indole-2-yl) acrylic acid methyl ester (XXXVI), which is treated successively with Na2S2O4, DIBAL, and finally with FeCl3, as before, to afford the dihydroxy quinone (XXII), already obtained.

1 Cotterill, A.S.; Moody, C.J.; Roffey, J.R.; An improved synthesis of the indolequinone anticancer agent EO9. Tetrahedron 1995, 51, 26, 7223-30.
2 Bailey, S.M.; Lohmeyer, M.; Dimbleby, R.; Castaner, J.; EO9. Drugs Fut 1996, 21, 2, 143.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
27698 methyl 2-(diethoxyphosphoryl)acetate 1067-74-9 C7H15O5P 详情 详情
(XXII) 12618 3-(Hydroxymethyl)-2-[(E)-3-hydroxy-1-propenyl]-5-methoxy-1-methyl-1H-indole-4,7-dione C14H15NO5 详情 详情
(XXIII) 10151 Ethyleneimine; Aziridine; Azirane 151-56-4 C2H5N 详情 详情
(XXIV) 12620 o-Vanillin; 2-Hydroxy-3-methoxybenzaldehyde 148-53-8 C8H8O3 详情 详情
(XXV) 12621 2-formyl-6-methoxyphenyl methanesulfonate C9H10O5S 详情 详情
(XXVI) 12622 2-formyl-6-methoxy-3-nitrophenyl methanesulfonate C9H9NO7S 详情 详情
(XXVII) 12623 methyl (E)-3-(2-hydroxy-3-methoxy-6-nitrophenyl)-2-propenoate C11H11NO6 详情 详情
(XXVIII) 12624 2-formyl-6-methoxy-3-nitrophenyl benzenesulfonate C14H11NO7S 详情 详情
(XXIX) 12625 methyl (E)-3-[2-(benzyloxy)-3-methoxy-6-nitrophenyl]-2-propenoate C18H17NO6 详情 详情
(XXX) 12626 methyl 4-(benzyloxy)-5-methoxy-1H-indole-2-carboxylate C18H17NO4 详情 详情
(XXXI) 12627 4-(Benzyloxy)-5-methoxy-1H-indole-2-carbaldehyde C17H15NO3 详情 详情
(XXXII) 12628 4-(Benzyloxy)-5-methoxy-1-methyl-1H-indole-2-carbaldehyde C18H17NO3 详情 详情
(XXXIII) 12629 ethyl (E)-3-[4-(benzyloxy)-5-methoxy-1-methyl-1H-indol-2-yl]-2-propenoate C22H23NO4 详情 详情
(XXXIV) 12630 ethyl (E)-3-[4-(benzyloxy)-3-formyl-5-methoxy-1-methyl-1H-indol-2-yl]-2-propenoate C23H23NO5 详情 详情
(XXXV) 12631 ethyl (E)-3-(3-formyl-4-hydroxy-5-methoxy-1-methyl-1H-indol-2-yl)-2-propenoate C16H17NO5 详情 详情
(XXXVI) 12632 ethyl (E)-3-(3-formyl-5-methoxy-1-methyl-4,7-dioxo-4,7-dihydro-1H-indol-2-yl)-2-propenoate C16H15NO6 详情 详情
Extended Information