Reaktion #73441

Reaktionsgleichung

4-{1-[5-(1-hydroxymethyl-cyclopropyl)-isoxazol-3-ylcarbamoyl]-1H-indol-5-yloxy}-5,7-dihydro-pyrrolo[3,4-d]pyrimidine-6-carboxylic acid tert-butyl ester

triethylamine

NH3

MeOH

TFA

→

title compound

5-(6,7-Dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-yloxy)-indole-1-carboxylic acid [5-(1-aminomethyl-cyclopropyl)-isoxazol-3-yl]-amide

Lösungsmittel

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigeis quenched with water
2. 2
   Extraktionthe organics extracted with EtOAc
3. 3
   Einengenconcentrationis
4. 4
   workup.DISSOLUTIONthen dissolved in THF (30 mL)
5. 5
   SonstigeAt this point the volatiles are removed
6. 6
   workup.DISSOLUTIONthe crude product is dissolved in DCM (10 mL)
7. 7
   SonstigeAfter 10 minutes the volatiles are removed in vacuo
8. 8
   workup.DISSOLUTIONThe product is dissolved in EtOAc
9. 9
   workup.ADDITIONNH4OH is added
10. 10
    SonstigeThe organics are removed
11. 11
    Sonstigethe crude product separated via FCC
12. 12
    Wascheneluting with DCM:MeOH:NH4OH (100:0:0 to 92:7:1)

Vorschrift

To a solution of 4-{1-[5-(1-hydroxymethyl-cyclopropyl)-isoxazol-3-ylcarbamoyl]-1H-indol-5-yloxy}-5,7-dihydro-pyrrolo[3,4-d]pyrimidine-6-carboxylic acid tert-butyl ester (500 mg, 0.939 mmol) in THF (10 mL), at 0° C., triethylamine (0.262 mL, 1.88 mmol) methanesulfonyl chloride (0.110 mL, 1.41 mmol) and DMAP (11.5 mg, 0.094 mmol) are added. After 2 h the reaction is complete and is quenched with water and the organics extracted with EtOAc. The crude product following concentrationis then dissolved in THF (30 mL), and NH3 in MeOH (1.82 mL, 12.8 mmol) is added. The reaction is stirred for 36 h. At this point the volatiles are removed and the crude product is dissolved in DCM (10 mL) and then TFA (10 mL, 130 mmol) is added. After 10 minutes the volatiles are removed in vacuo. The product is dissolved in EtOAc and then NH4OH is added. The organics are removed and the crude product separated via FCC eluting with DCM:MeOH:NH4OH (100:0:0 to 92:7:1) to give the title compound. MS (ESI) m/z 432.0 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.55 (s, 1 H)8.35 (d, J=8.84 Hz, 1 H)8.15 (d, J=3.54 Hz, 1 H)7.44 (d, J=2.53 Hz, 1 H)7.11 (dd, J=9.09, 2.53 Hz, 1 H)6.77 (s, 1 H)6.70 (d, J=4.04 Hz, 1 H)4.09 (d, J=11.87 Hz, 4 H)2.94 (s, 2 H)1.05 (d, J=3.03 Hz, 4 H).

Quelle