反应 #45525

反应方程式

N-[4-(4-amino-7-iodothieno [3,2-c]pyridin-3-yl)-2-methoxyphenyl]-1-methyl-1H-indole-2-carboxamide

copper(I) cyanide

→

title compound

收率 25.0%

N-[4-(4-amino-7-cyanothieno [3,2-c]pyridin-3-yl)-2-methoxyphenyl]-1-methyl-1H-indole-2-carboxamide

收率 25.0%

溶剂

1,4-dioxane

反应条件

后处理

1. 1
   其他The mixture was evaporated in vacuo
2. 2
   workup.ADDITIONdiluted with dichloromethane/methanol (95:5, 50 mL)
3. 3
   洗涤washed with ammonium hydroxide (8% aqueous, 8 mL)
4. 4
   洗涤The aqueous layer was washed with dichloromethane/methanol (95:5, 10 mL)
5. 5
   其他the combined organics were evaporated in vacuo
6. 6
   workup.ADDITIONdiluted with dimethylforamide (2.5 mL)
7. 7
   过滤filtered
8. 8
   其他The precipitate was triturated in acetic acid (3 mL)
9. 9
   过滤filtered

实验过程

N-[4-(4-amino-7-iodothieno [3,2-c]pyridin-3-yl)-2-methoxyphenyl]-1-methyl-1H-indole-2-carboxamide (A-796259.0, 100 mg, 0.36 mmol), copper(I) cyanide (65 mg, 0.72 mmol), tetraethylammonium cyanide (28 mg, 0. 18 mmol), Tris(dibenzylideneacetone)-dipalladium(0) (7 mg, 0.007 mmol), and 1,1′-bis(diphenylphosphino)ferrocene (16 mg, 0.029 mmol) were purged and heated to 110° C. in 1,4-dioxane (2 mL) for 16 hours. The mixture was evaporated in vacuo, diluted with dichloromethane/methanol (95:5, 50 mL), and washed with ammonium hydroxide (8% aqueous, 8 mL). The aqueous layer was washed with dichloromethane/methanol (95:5, 10 mL), and the combined organics were evaporated in vacuo, diluted with dimethylforamide (2.5 mL), and filtered. The precipitate was triturated in acetic acid (3 mL) and filtered to yield the title compound (20 mg, 25% yield): 1H NMR (DMSO, 400 MHz) δ 9.49 (s, 1H), 8.44 (s, 1H), 8.03 (d, 1H), 7.76 (s, 1H), 7.70 (d, 1H), 7.56 (d, 1H), 7.05-7.33 (m, 5H), 4.01 (s, 3H), 3.89 (s, 3H); RP-HPLC (Conditions i) Rt 24.9 min. MS: 452.2 MH−.

来源