Reacción #45474

Ecuación de reacción

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

2-[(E)-3,3-diethoxy-1-propenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

sodium carbonate

p-toluenesulfonic acid monohydrate

2-[(E)-3,3-diethoxy-1-propenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

sodium carbonate

→

title compound

Rendimiento 36.9%

N-(4-{4-amino-7-[(1E)-3-oxoprop-1-enyl]furo[3,2-c]pyridin-3-yl}-2-methoxyphenyl)-1-methyl-1H-benzimidazole-2-carboxamide

Rendimiento 36.9%

Disolventes

1,2-dimethoxyethane

water

water

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturathe mixture was heated for another 24 hours
2. 2
   Temperaturathe mixture was heated for another 24 hours after which time all starting material
3. 3
   Otrowas consumed
4. 4
   OtroThe solvent was removed in vacuo
5. 5
   Otrothe residue was triturated with water (30 mL) for 3 hours
6. 6
   FiltraciónThe solid was collected by filtration
7. 7
   Otrodried in vacuo
8. 8
   OtroThe acetone was removed in vacuo
9. 9
   Filtraciónthe precipitate was filtered
10. 10
    Lavadowashing with water
11. 11
    OtroThe precipitate was triturated with 2-propanol (30 mL) for 1 hour
12. 12
    OtroThe solvent was removed an the residue
13. 13
    Otrowas partitioned between dichloromethane (20 mL) and water (40 mL)
14. 14
    SecadoThe organic layer was dried over anhydrous magnesium sulfate
15. 15
    Otrothe solvent was removed in vacuo

Procedimiento

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.

Fuente