Réaction #45473

Équation de réaction

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

Rendement 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

Rendement 62.0%

Solvants

acetone

water

1,2-dimethoxyethane

water

Conditions de réaction

Traitement

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

Mode opératoire

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.

Source