반응 #45474

ord-243024e82f2243f2871d2863333f8cf7

반응 조건

상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    온도the mixture was heated for another 24 hours
  2. 2
    온도the mixture was heated for another 24 hours after which time all starting material
  3. 3
    기타was consumed
  4. 4
    기타The solvent was removed in vacuo
  5. 5
    기타the residue was triturated with water (30 mL) for 3 hours
  6. 6
    여과The solid was collected by filtration
  7. 7
    기타dried in vacuo
  8. 8
    기타The acetone was removed in vacuo
  9. 9
    여과the precipitate was filtered
  10. 10
    세척washing with water
  11. 11
    기타The precipitate was triturated with 2-propanol (30 mL) for 1 hour
  12. 12
    기타The solvent was removed an the residue
  13. 13
    기타was partitioned between dichloromethane (20 mL) and water (40 mL)
  14. 14
    건조The organic layer was dried over anhydrous magnesium sulfate
  15. 15
    기타the solvent was removed in vacuo

실험 절차

A mixture of N-[4-(4-amino-7-iodofuro[3,2-c]pyridin-3-yl)-2-methoxyphenyl]-1-methyl-1H-benzimidazole-2-carboxamide (1.50 g, 2.78 mmol) in 1,2-dimethoxyethane (30 mL) and water (15 mL) was reacted 2-[(E)-3,3-diethoxy-1-propenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.42 g, 5.56 mmol,), sodium carbonate (1.17 g, 11.12 mmol) and tetrakis triphenylphosphine palladium (0) (0.19 g, 0.17 mmol) at 80° C. for 18 hours. Additional 2-[(E)-3,3-diethoxy-1-propenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.00 g, 3.90 mmol,), sodium carbonate (0.508 g, 4.80 mmol) and tetrakis triphenylphosphine palladium (0) (0.19 g, 0.17 mmol) was added and the mixture was heated for another 24 hours. Additional tetrakis triphenylphosphine palladium (0) (0.32 g, 0.27 mmol) was added and the mixture was heated for another 24 hours after which time all starting material was consumed. The solvent was removed in vacuo and the residue was triturated with water (30 mL) for 3 hours. The solid was collected by filtration and dried in vacuo. The crude product was suspended in acetone (60 mL) and water (8 mL) and reacted with p-toluenesulfonic acid monohydrate (0.10 g, 0.52 mmol) 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 solvent was removed an the residue was partitioned between dichloromethane (20 mL) and water (40 mL). The organic layer was dried over anhydrous magnesium sulfate and the solvent was removed in vacuo to give the title compound (0.48 g, 31%) as a yellow solid. 1H NMR (DMSO-d6, 400 MHz) δ 10.19 (s, 1H), 9.64 (d, 1H), 8.52 (dd, 1H), 8.26 (s, 1H), 8.21 (s, 1H), 7.86 (d, 1H), 7.75-7.82 (m, 2H), 7.47 (t, 1H), 7.39 (t, 1H), 7.32 (d, 1H), 7.21 (dd, 1H), 6.93 (dd, 1H), 4.25 (s, 3H), 4.04 (s, 3H), 1.86 (s, 3H); RP-HPLC (Conditions g) Rt 12.21 min.; MS: MH+ 468.

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US07737160B2uspto-grants-2010_06