Trifluoroacetic acid → 6-fluoro-5-(5-methyl-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-ylamine

HRID 1396151노트

반응식

HRID 1396151 반응식
C(OC(=O)[N:7]([C:17]1[CH:22]=[CH:21][C:20]([CH:23](O)[C:24]2[C:32]3[C:27](=[N:28][CH:29]=[C:30]([CH3:33])[CH:31]=3)[N:26]([Si](C(C)C)(C(C)C)C(C)C)[CH:25]=2)=[C:19]([F:45])[N:18]=1)CC1C=CC(OC)=CC=1)(C)(C)C.C([SiH](CC)CC)C.FC(F)(F)C(O)=O>C(#N)C>[F:45][C:19]1[N:18]=[C:17]([NH2:7])[CH:22]=[CH:21][C:20]=1[CH2:23][C:24]1[C:32]2[C:27](=[N:28][CH:29]=[C:30]([CH3:33])[CH:31]=2)[NH:26][CH:25]=1

참가 물질

5

반응물 3

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 58258936{6-fluoro-5-[hydroxy-(5-methyl-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-methyl]-pyridin-2-yl}-(4-methoxy-benzyl)-carbamic acid tert-butyl ester

생성물 1

HCID 582592126-fluoro-5-(5-methyl-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-ylamine수율 62.7%

시약·촉매·용매 1

HCID 6342Acetonitrile용매

반응 조건

온도
50 °C

실험 절차

To {6-fluoro-5-[hydroxy-(5-methyl-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-methyl]-pyridin-2-yl}-(4-methoxy-benzyl)-carbamic acid tert-butyl ester (48, 21 g, 32.4 mmol) in 500 mL of acetonitrile, triethylsilane (51.7 mL, 324 mmol) and trifluoroacetic acid (24.93 mL, 324 mmol) are added. The reaction is stirred at 50° C. for several hours, then concentrated under vacuum, and the residue is taken up in 250 mL of dichloromethane and 250 mL of trifluoroacetic acid is added. The mixture is stirred at reflux for several hours, then concentrated under vacuum. The residue is taken up in ethyl acetate and poured into aqueous potassium carbonate. The organic layer is separated, concentrated under vacuum and purified by silica gel column chromatography, eluting with 0-5% methanol in dichloromethane. Appropriate fractions are combined and the solvents removed under vacuum to provide the desired compound (49, 5.2 g, 20.29 mmol, 62.7% yield).

후처리

  1. concentrationconcentrated under vacuum
  2. addition250 mL of trifluoroacetic acid is added
  3. stirringThe mixture is stirred
  4. temperatureat reflux for several hours
  5. concentrationconcentrated under vacuum
  6. additionpoured into aqueous potassium carbonate
  7. customThe organic layer is separated
  8. concentrationconcentrated under vacuum
  9. custompurified by silica gel column chromatography
  10. washeluting with 0-5% methanol in dichloromethane
  11. customthe solvents removed under vacuum

출처 및 근거

ORD 기록
ord-09d15cc7905c4be5ad14f196ca6f1c43
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08901118B2

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