Reaktion #73378

Reaktionsgleichung

t-butyl bromoacetate

5-(6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-yloxy)-N-(3-(trifluoromethyl)phenyl)-1H-indole-1-carboxamide

DMF

→

TFA

Ausbeute 0.1%

{4-[1-(3-Trifluoromethyl-phenylcarbamoyl)-1H-indol-5-yloxy]-5,7-dihydro-pyrrolo[3,4-d]pyrimidin-6-yl}-acetic acid

Reaktionsbedingungen

Aufarbeitung

1. 1
   EinengenThe reaction is concentrated
2. 2
   workup.ADDITIONdiluted with DCM (10 mL)
3. 3
   Temperaturcooled to 0° C
4. 4
   workup.ADDITIONTFA (5 mL) is then added
5. 5
   Sonstigethe ice bath is removed
6. 6
   workup.STIRRINGthe reaction is stirred at room temperature
7. 7
   EinengenThe reaction is concentrated
8. 8
   workup.ADDITIONdiluted with ethyl acetate
9. 9
   workup.ADDITIONThe solution is then treated with 1N HCl
10. 10
    SonstigeThe ethyl acetate is removed
11. 11
    Sonstigedried
12. 12
    Einengenconcentrated to a residue
13. 13
    workup.DISSOLUTIONThe residue is dissolved in DMSO
14. 14
    Sonstigepurified via HPLC (C18

Vorschrift

5-(6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-yloxy)-N-(3-(trifluoromethyl)phenyl)-1H-indole-1-carboxamide (121.9 mg, 0.277 mmol) is dissolved in DMF (5 mL) and TEA (200 μl, 1.435 mmol) is added followed by t-butyl bromoacetate (101 μl, 0.693 mmol). The solution is stirred at rt overnight. The reaction is concentrated and then diluted with DCM (10 mL) and cooled to 0° C. TFA (5 mL) is then added and the ice bath is removed and the reaction is stirred at room temperature. The reaction is concentrated, basified with ammonium hydroxide, and diluted with ethyl acetate. The solution is then treated with 1N HCl. The ethyl acetate is removed, dried and concentrated to a residue. The residue is dissolved in DMSO and purified via HPLC (C18; 20-100% I/H2O with 0.1% TFA to obtain {4-[1-(3-Trifluoromethyl-phenylcarbamoyl)-1H-indol-5-yloxy]-5,7-dihydro-pyrrolo[3,4-d]pyrimidin-6-yl}-acetic acid. MS (ESI) m/z 498.9 (M+1); 1H NMR (400 MHz, MeOD) δ ppm 8.50 (s, 1 H)8.32 (d, J=8.84 Hz, 1 H)8.06 (s, 1 H)7.88-7.95 (m, 2 H)7.57 (t, J=7.96 Hz, 1 H)7.40-7.45 (m, 2 H)7.12 (dd, J=9.09, 2.02 Hz, 1 H)6.74 (d, J=3.79 Hz, 1 H)4.19 (d, J=9.35 Hz, 4 H), 3.43 (s, 2H).

Quelle