反応 #73369

反応方程式

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

溶媒

THF

反応条件

後処理

1. 1
   その他flushed with nitrogen
2. 2
   workup.STIRRINGto stir at room temperature overnight
3. 3
   温度The reaction is cooled in an ice bath
4. 4
   その他quenched with a saturated solution of ammonium chloride (100 mL)
5. 5
   workup.ADDITIONThe mixture is then diluted with ethyl acetate
6. 6
   抽出the product is extracted (2×100 mL EtOAc)
7. 7
   その他dried
8. 8
   濃縮concentrated to a brown oil that
9. 9
   workup.DISSOLUTIONis dissolved in 10 mL of DCM
10. 10
    温度cooled in an ice bath
11. 11
    workup.ADDITION10 mL of TFA is added
12. 12
    その他completion of the reaction the DCM and TFA
13. 13
    その他are removed
14. 14
    workup.ADDITIONethyl acetate is added to the residue along with ammonium hydroxide
15. 15
    その他to quench the remaining TFA
16. 16
    workup.ADDITIONThe mixture is diluted with water
17. 17
    抽出extracted with ethyl acetate (2×50 mL)
18. 18
    その他The organic layers are removed
19. 19
    その他dried
20. 20
    濃縮concentrated
21. 21
    その他The residue is absorbed onto silica
22. 22
    その他separated via FCC (0-6% Methanol/DCM)

実験手順

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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