반응 #73369

반응 방정식

Tert-butyl 4-(1H-indol-5-yloxy)-5H-pyrrolo[3,4-d]pyrimidine-6(7 H)-carboxylate

Sodium hydride

Phenyl 5-tert-butylisoxazol-3-ylcarbamate

→

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

용매

THF

반응 조건

후처리

1. 1
   기타flushed with nitrogen
2. 2
   workup.STIRRINGto stir at room temperature overnight
3. 3
   온도The reaction is cooled in an ice bath
4. 4
   기타quenched with a saturated solution of ammonium chloride (100 mL)
5. 5
   workup.ADDITIONThe mixture is then diluted with ethyl acetate
6. 6
   추출the product is extracted (2×100 mL EtOAc)
7. 7
   기타dried
8. 8
   농축concentrated to a brown oil that
9. 9
   workup.DISSOLUTIONis dissolved in 10 mL of DCM
10. 10
    온도cooled in an ice bath
11. 11
    workup.ADDITION10 mL of TFA is added
12. 12
    기타completion of the reaction the DCM and TFA
13. 13
    기타are removed
14. 14
    workup.ADDITIONethyl acetate is added to the residue along with ammonium hydroxide
15. 15
    기타to quench the remaining TFA
16. 16
    workup.ADDITIONThe mixture is diluted with water
17. 17
    추출extracted with ethyl acetate (2×50 mL)
18. 18
    기타The organic layers are removed
19. 19
    기타dried
20. 20
    농축concentrated
21. 21
    기타The residue is absorbed onto silica
22. 22
    기타separated via FCC (0-6% Methanol/DCM)

실험 절차

Tert-butyl 4-(1H-indol-5-yloxy)-5H-pyrrolo[3,4-d]pyrimidine-6(7 H)-carboxylate (127 mg, 0.360 mmol) is dissolved in THF (8 mL), flushed with nitrogen and cooled to 0° C. Sodium hydride (23 mg, 0.575 mmol, 60% in mineral oil) is added and the mixture is stirred for 10 minutes. Phenyl 5-tert-butylisoxazol-3-ylcarbamate (140 mg, 0.538 mmol) is added neat and the reaction is allowed to stir at room temperature overnight. The reaction is cooled in an ice bath and quenched with a saturated solution of ammonium chloride (100 mL). The mixture is then diluted with ethyl acetate and the product is extracted (2×100 mL EtOAc). The organic layers are combined, dried and concentrated to a brown oil that is dissolved in 10 mL of DCM and cooled in an ice bath and 10 mL of TFA is added. Following completion of the reaction the DCM and TFA are removed and ethyl acetate is added to the residue along with ammonium hydroxide to quench the remaining TFA. The mixture is diluted with water and extracted with ethyl acetate (2×50 mL). The organic layers are removed, dried, and concentrated. The residue is absorbed onto silica and separated via FCC (0-6% Methanol/DCM) to obtain N-(5-tert-butylisoxazol-3-yl)-5-(6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-yloxy)-1H-indole-1-carboxamide. MS (ESI) m/z 419.2 (M+1); 1H NMR (400 MHz, DMSO-d6) δ ppm 8.56 (s, 1 H)8.29 (d, J=8.84 Hz, 1 H)8.17 (d, J=3.79 Hz, 1 H)7.47 (d, J=2.27 Hz, 1 H)7.15 (dd, J=8.97, 2.40 Hz, 1 H)6.76 (d, J=3.28 Hz, 1 H)6.68 (s, 1 H)4.07-4.14 (m, 4 H)1.34 (s, 9 H).

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