반응 #45473
ord-a15ea47583164bc2b21782918c1a01a4
반응 방정식
반응물
시약
반응 조건
후처리
- 1기타The solvent was removed in vacuo
- 2기타the residue was partitioned between ethyl acetate (15 mL) and water (30 mL)
- 3기타The layers were separated
- 4추출the aqueous layer was extracted with ethyl acetate (2×15 mL)
- 5건조The combined organic layers were dried over anhydrous magnesium sulfate
- 6기타the solvent was removed in vacuo
- 7기타The residue was purified by flash column chromatography on silica gel using 10% methanol in dichloromethane as an eluent
- 8기타to give
- 9기타The acetone was removed in vacuo
- 10여과the precipitate was filtered
- 11세척washing with water
- 12기타The precipitate was triturated with 2-propanol (30 mL) for 1 hour
- 13여과The solid was filtered
- 14기타dried in vacuo
실험 절차
A mixture of N-[4-(4-amino-7-iodofuro[3,2-c]pyridin-3-yl)-2-methoxyphenyl]-1-methyl-1H-indole-2-carboxamide (3.16 g, 5.86 mmol) in 1,2-dimethoxyethane (40 mL) and water (20 mL) was reacted 2-[(E)-3,3-diethoxy-1-propenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (2.87 g, 7.03 mmol,), sodium carbonate (1.55 g, 14.66 mmol) and tetrakis triphenylphosphine palladium (0) (0.68 g, 0.59 mmol) at 80° C. for eighteen hours. The solvent was removed in vacuo and the residue was partitioned between ethyl acetate (15 mL) and water (30 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (2×15 mL). The combined organic layers were dried over anhydrous magnesium sulfate and the solvent was removed in vacuo. The residue was purified by flash column chromatography on silica gel using 10% methanol in dichloromethane as an eluent to give a mixture of diethyl acetal, methyl ethyl acetal, and aldehyde. This mixture was reacted with p-toluenesulfonic acid monohydrate (0.10 g, 0.53 mmol) in acetone (100 mL) and water (10 mL) at ambient temperature for eighteen hours. The acetone was removed in vacuo and the precipitate was filtered, washing with water. The precipitate was triturated with 2-propanol (30 mL) for 1 hour. The solid was filtered and dried in vacuo to give the title compound (1.690 g, 62%) as a yellow solid. 1H NMR (DMSO-d6, 400 MHz) 9.64 (d, 1H), 9.49 (s, 1H), 8.26 (s, 1H), 8.22 (s, 1H), 8.06 (t, 1H), 7.79 (d, 1H), 7.71 (d, 1H), 7.59 (d, 1H), 7.30-7.38 (m, 2H), 7.27 (d, 1H), 7.12-7.20 (m, 2H), 6.94 (dd, 1H), 6.33-6.59 (b, 2H), 4.04 (s, 3H), 3.94 (s, 3H); RP-HPLC (Conditions d) Rt 7.36 min.; MS: MH30 467.