反応 #45525

反応方程式

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

収率 25.0%

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

収率 25.0%

溶媒

1,4-dioxane

反応条件

後処理

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

実験手順

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−.

出典