反応 #73443

反応方程式

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

溶媒

brine

DCM

DCE

反応条件

後処理

1. 1
   抽出the product is extracted with EtOAc
2. 2
   その他The organics are dried
3. 3
   その他evaporated
4. 4
   その他to give the crude product
5. 5
   その他After 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
   その他The organics are removed
9. 9
   その他the crude product separated via FCC
10. 10
    洗浄eluting with DCM:MeOH:NH4OH (100:0:0 to 92:7:1)

実験手順

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).

出典