Reacción #45473

Ecuación de reacción

p-toluenesulfonic acid monohydrate

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

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

sodium carbonate

→

title compound

Rendimiento 62.0%

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

Rendimiento 62.0%

Disolventes

acetone

water

1,2-dimethoxyethane

water

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroThe solvent was removed in vacuo
2. 2
   Otrothe residue was partitioned between ethyl acetate (15 mL) and water (30 mL)
3. 3
   OtroThe layers were separated
4. 4
   Extracciónthe aqueous layer was extracted with ethyl acetate (2×15 mL)
5. 5
   SecadoThe combined organic layers were dried over anhydrous magnesium sulfate
6. 6
   Otrothe solvent was removed in vacuo
7. 7
   OtroThe residue was purified by flash column chromatography on silica gel using 10% methanol in dichloromethane as an eluent
8. 8
   Otroto give
9. 9
   OtroThe acetone was removed in vacuo
10. 10
    Filtraciónthe precipitate was filtered
11. 11
    Lavadowashing with water
12. 12
    OtroThe precipitate was triturated with 2-propanol (30 mL) for 1 hour
13. 13
    FiltraciónThe solid was filtered
14. 14
    Otrodried in vacuo

Procedimiento

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.

Fuente