Reaktion #73443

Reaktionsgleichung

TFA

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

dimethylamine

sodium triacetoxyborohydride

→

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

Lösungsmittel

brine

DCM

DCE

Reaktionsbedingungen

Aufarbeitung

1. 1
   Extraktionthe product is extracted with EtOAc
2. 2
   SonstigeThe organics are dried
3. 3
   Sonstigeevaporated
4. 4
   Sonstigeto give the crude product
5. 5
   SonstigeAfter 10 minutes the volatiles are removed in vacuo
6. 6
   workup.DISSOLUTIONThe product is dissolved in EtOAc
7. 7
   workup.ADDITIONNH4OH is added
8. 8
   SonstigeThe organics are removed
9. 9
   Sonstigethe crude product separated via FCC
10. 10
    Wascheneluting with DCM:MeOH:NH4OH (100:0:0 to 92:7:1)

Vorschrift

To a solution of 4-{1-[5-(1-formyl-cyclopropyl)-isoxazol-3-ylcarbamoyl]-1H-indol-5-yloxy}-5,7-dihydro-pyrrolo[3,4-d]pyrimidine-6-carboxylic acid tert-butyl ester (120 mg, 0.226 mmol) in DCE (2 ml), dimethylamine (0.34 mL, 0.679 mmol) and sodium triacetoxyborohydride (192 mg, 0.905 mmol) are added. After 2 h the reaction is complete, brine is added and the product is extracted with EtOAc. The organics are dried and evaporated to give the crude product. The mixture is diluted with 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 5-(6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-yloxy)-indole-1-carboxylic acid [5-(1-dimethylaminomethyl-cyclopropyl)-isoxazol-3-yl]-amide. MS (ESI) m/z 460.9 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.55 (s, 1 H)8.29 (d, J=8.84 Hz, 1 H)8.16 (d, J=3.79 Hz, 1 H)7.47 (d, J=2.27 Hz, 1 H)7.16 (s, 1 H)6.82 (s, 1 H)6.75 (d, J=4.04 Hz, 1 H)4.06-4.15 (m, 1 H)2.57 (s, 2 H)2.20 (s, 6 H)1.17 (d, J=2.27 Hz, 2 H)0.93 (d, J=2.27 Hz, 2 H).

Quelle