Reaktion #327961

Reaktionsgleichung

water

5-bromo-1H-indazol-3-amine

sodium carbonate

solution

3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)propanenitrile

→

title compound

3-[4-(3-amino-1H-indazol-5-yl)-1H-pyrazol-1-yl]propanenitrile

Lösungsmittel

acetonitrile

1,2-dimethoxyethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   Einengenthe mixture was concentrated under reduced pressure
2. 2
   workup.ADDITIONMethanol (20 mL) was added
3. 3
   SonstigeThe insoluble material was removed by filtration
4. 4
   EinengenThe filtrate was concentrated under reduced pressure onto silica gel
5. 5
   Sonstigepurified via silica gel chromatography
6. 6
   Wascheneluting with a stepwise gradient of dichloromethane/methanol/ammonium hydroxide (990:9:1 to 985:13.5:1.5 to 980:18:2)
7. 7
   Sonstigeto afford a solid
8. 8
   Filtrationfiltered
9. 9
   Sonstigeto remove minor amount of insolubles
10. 10
    Waschenwhile washing with methanol (<0.5 mL)
11. 11
    workup.WAITleft
12. 12
    Sonstigeto sit at ambient temperature
13. 13
    SonstigeThe resulting solid that formed overnight
14. 14
    Filtrationwas collected by filtration
15. 15
    Waschenwhile washing with additional acetonitrile
16. 16
    Sonstigedried in a vacuum oven at about 60° C. for about 2 hours

Vorschrift

To a microwave vial was added 5-bromo-1H-indazol-3-amine (0.14 g, 0.66 mmol), tetrakis(triphenylphosphine)palladium(0) (0.076 g, 0.066 mmol), and sodium carbonate (0.147 g, 1.39 mmol) followed by a solution of Example 267A (0.212 g, 0.858 mmol) in 1,2-dimethoxyethane (2.50 mL) and then water (1.25 mL). The mixture was heated in a CEM microwave at about 150° C. for about 20 minutes (275 psi maximum pressure, about 2 minutes ramp, 200 maximum watts) and then the mixture was concentrated under reduced pressure. Methanol (20 mL) was added and the resulting mixture was stirred for about 1 hour. The insoluble material was removed by filtration. The filtrate was concentrated under reduced pressure onto silica gel and purified via silica gel chromatography eluting with a stepwise gradient of dichloromethane/methanol/ammonium hydroxide (990:9:1 to 985:13.5:1.5 to 980:18:2) to afford a solid. This solid was dissolved in a minimum amount of hot acetonitrile (˜2 mL), filtered to remove minor amount of insolubles, while washing with methanol (<0.5 mL), and left to sit at ambient temperature. The resulting solid that formed overnight was collected by filtration, while washing with additional acetonitrile, and dried in a vacuum oven at about 60° C. for about 2 hours to afford the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.35 (s, 1H), 8.10 (s, 1H), 7.86 (s, 1H), 7.84 (s, 1H), 7.44 (dd, J=8.54, 1.26 Hz, 1H), 7.23 (d, J=8.62 Hz, 1H), 5.32 (s, 2H), 4.42 (t, J=6.36 Hz, 2H), 3.10 (t, J=6.43 Hz, 2H). MS (ESI+) m/z 253.2 (M+H)+.

Quelle