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

【结 构 式】

【分子编号】39296

【品名】2-(1-methyl-6-nitro-1H-indol-3-yl)-2-oxoacetyl chloride

【CA登记号】

【 分 子 式 】C11H7ClN2O4

【 分 子 量 】266.64036

【元素组成】C 49.55% H 2.65% Cl 13.3% N 10.51% O 24%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(III)

6-Nitroindole (I) was methylated using iodomethane and NaH and the resulting 1-methyl-6-nitroindole (II) was acylated with oxalyl chloride in dichloromethane to furnish the glyoxylyl chloride (III). Subsequent condensation of (III) with 1-methylindole-3-acetic acid (IV) in the presence of Et3N gave the bisindolylmaleic anhydride (V). This was finally converted into the target maleimide by heating with ammonia in aqueous DMF in a sealed vessel at 140 C.

1 Hill, C.H.; Wilkinson, S.E.; Hurst, S.A.; Lawton, G.; Keech, E.; Davis, P.D.; Nixon, J.S.; Turner, S.E.; Inhibitors of protein kinase C. 1. 2,3-Bisarylmaleimides. J Med Chem 1992, 35, 1, 177.
2 Davis, P.D.; Hill, C.H.; Lawton, G. (F. Hoffmann-La Roche AG); Substd. pyrroles. AU 8929658; EP 0328026; JP 1989233281; US 5057614 .
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) 39294 6-Nitroindole; 6-Nnitro-1H-indole 4769-96-4 C8H6N2O2 详情 详情
(II) 39295 1-methyl-6-nitro-1H-indole C9H8N2O2 详情 详情
(III) 39296 2-(1-methyl-6-nitro-1H-indol-3-yl)-2-oxoacetyl chloride C11H7ClN2O4 详情 详情
(IV) 39297 1-Methylindole-3-acetic acid; 2-(1-Methyl-1H-indol-3-yl)acetic acid 1912-48-7 C11H11NO2 详情 详情
(V) 39298 3-(1-methyl-1H-indol-3-yl)-4-(1-methyl-6-nitro-1H-indol-3-yl)-2,5-furandione C22H15N3O5 详情 详情
(VI) 29841 Oxalyl chloride; 2-Chloro-2-oxoacetyl chloride 79-37-8 C2Cl2O2 详情 详情

合成路线2

该中间体在本合成路线中的序号:(III)

Methylation of 6-nitroindole (I) using either iodomethane and NaH or dimethyl carbonate and Na2CO3 provides 1-methyl-6-nitroindole (II), which is subsequently acylated with oxalyl chloride in CH2Cl2 to furnish the glyoxylyl chloride (III). Condensation of chloride (III) with 1-methylindole-3-acetic acid (IV) in the presence of Et3N gives the bis(indolyl)maleic anhydride (V), which is then converted to the target maleimide derivative by heating with ammonia in aqueous DMF in a sealed vessel at 140 °C .
In a related procedure, quaternization of 3-(dimethylaminomethyl)-indole (VI) with butyl bromide, followed by amine displacement with NaCN yields 2-(3-indolyl)acetonitrile (VII), which is alkylated using dimethyl carbonate and K2CO3 in hot DMF to give the 1-methylindole derivative (VIII). Treatment of compound (VIII) with isopropanol and HCl (generated from acetyl chloride and i-PrOH) affords imidate (IX), which is finally condensed with the indoleglyoxylyl chloride (III) in the presence of DIEA, followed by treatment with H2SO4 .

1 Davis, P.D., Hill, C.H., Lawton, G. (F. Hoffmann-La Roche AG). Substituted pyrroles. AU 8929658, EP 0328026, JP 1989233281, US 5057614.
2 Davis, P.D., Hill, C.H., Lawton, G. et al. Inhibitors of protein kinase C. 1. 2,3-Bisarylmaleimides. J Med Chem 1992, 35(1): 177-84.
3 Jiang, X. (F. Hoffmann La Roche AG). Methylation of indole compounds using dimethyl carbonate. CA 2405937, EP 1276721, JP 2003531192, JP 2007254487, US 6326501, WO 2001081305.
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) 39294 6-Nitroindole; 6-Nnitro-1H-indole 4769-96-4 C8H6N2O2 详情 详情
(II) 39295 1-methyl-6-nitro-1H-indole C9H8N2O2 详情 详情
(III) 39296 2-(1-methyl-6-nitro-1H-indol-3-yl)-2-oxoacetyl chloride C11H7ClN2O4 详情 详情
(IV) 39297 1-Methylindole-3-acetic acid; 2-(1-Methyl-1H-indol-3-yl)acetic acid 1912-48-7 C11H11NO2 详情 详情
(V) 39298 3-(1-methyl-1H-indol-3-yl)-4-(1-methyl-6-nitro-1H-indol-3-yl)-2,5-furandione C22H15N3O5 详情 详情
(VI) 37568 N,N-Dimethyl-1H-indole-3-methanamine;Gramine;N-(1H-indol-3-ylmethyl)-N,N-dimethylamine; 3-(dimethylaminomethyl)-indole[;]1H-indol-3-yl-N,N-dimethylmethanamine 87-52-5 C11H14N2 详情 详情
(VII) 44291 3-Indolylacetonitrile;3-Cyanomethyl-1H-indole;3-(Cyanomethyl)indole;Indole-3-acetonitrile;3-Indoleacetonitrile;2-(3-indolyl)acetonitrile;2-(1H-indol-3-yl)acetonitrile;2-(1H-Indol-3-yl)acetonitrile; 3-Indolylacetonitrile 771-51-7 C10H8N2 详情 详情
(VIII) 69305 1-Methylindole-3-acetonitrile;1-Methylindole-3-acetonitrile;N-Methylindole-3-acetonitrile;3-(Cyanomethyl)-1-methylindole;2-(1-methyl-1H-indol-3-yl)acetonitrile 51584-17-9 C11H10N2 详情 详情
(IX) 69306 isopropyl 2-(1-methyl-1H-indol-3-yl)acetimidate hydrochloride   C14H18N2O.HCl 详情 详情
Extended Information