반응 #333432

ord-186476861138432f9c6b5794e599829b

용매

반응 조건

온도
0°CELSIUS
상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    기타to give a yellow solution
  2. 2
    workup.STIRRINGthe reaction was stirred at 0° C. for 30 min
  3. 3
    온도to warm to room temperature
  4. 4
    workup.STIRRINGstirred for 2 h
  5. 5
    기타The reaction mixture was quenched with 5 mL of brine and 10 mL of water
  6. 6
    추출extracted with ethyl acetate (2×30 mL)
  7. 7
    세척The combined organic layers were washed with water and brine
  8. 8
    기타dried
  9. 9
    농축concentrated in vacuo
  10. 10
    기타The crude material was purified by silica gel chromatography (0-10% methanol in dichloromethane)

실험 절차

2-(6-Chloro-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-methoxy-1-methyl-ethyl)-amide (80 mg, 0.16 mmol) was combined with DMF (8 mL) at 0° C. to give a yellow solution. Sodium hydride (60% in mineral oil, 19 mg, 0.47 mmol) was added and the reaction was stirred at 0° C. for 10 min. Dimethylaminoethyl bromide hydrobromide (54 mg, 0.23 mmol) was added and the reaction was stirred at 0° C. for 30 min, then allowed to warm to room temperature and stirred for 2 h. The reaction mixture was quenched with 5 mL of brine and 10 mL of water, then extracted with ethyl acetate (2×30 mL). The combined organic layers were washed with water and brine, then dried and concentrated in vacuo. The crude material was purified by silica gel chromatography (0-10% methanol in dichloromethane) to afford 50 mg (55%) of 2-[6-chloro-1-(2-dimethylamino-ethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-methoxy-1-methyl-ethyl)-amide as a foaming solid. MS: (M+H)+=587.

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US08658646B2uspto-grants-2014_02