Hydrochloric Acid → 4-(1H-pyrazol-4-yl)-5-fluoro-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridine

HRID 1617373노트

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HRID 1617373 반응식
[F:1][C:2]1[C:3](I)=[C:4]2[CH:10]=[CH:9][N:8]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[C:5]2=[N:6][CH:7]=1.C(OC([N:25]1[CH:29]=[C:28](B2OC(C)(C)C(C)(C)O2)[CH:27]=[N:26]1)C)C.C(=O)([O-])[O-].[Na+].[Na+].Cl.[OH-].[Na+]>O1CCOCC1.O.CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1COCC1>[NH:25]1[CH:29]=[C:28]([C:3]2[C:2]([F:1])=[CH:7][N:6]=[C:5]3[N:8]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[CH:9]=[CH:10][C:4]=23)[CH:27]=[N:26]1

참가 물질

11

반응물 5

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 14798Sodium HydroxideHCID 467367981-(1-Ethoxyethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 584313555-fluoro-4-iodo-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridine

생성물 1

HCID 584313954-(1H-pyrazol-4-yl)-5-fluoro-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridine수율 69%

시약·촉매·용매 5

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매2회HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

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온도
110 °C

실험 절차

A mixture of 5-fluoro-4-iodo-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridine (7.20 g, 18.4 mmol), 1-(1-ethoxyethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (5.36 g, 20.1 mmol), tetrakis(triphenylphosphine)palladium(0) (1.06 g, 0.918 mmol) and sodium carbonate (5.84 g, 55.1 mmol) in 1,4-dioxane (50 mL) and water (25 mL) was stirred at 110° C. under nitrogen for 1 hour. After being cooled to room temperature, the mixture was diluted with EtOAc, washed with water and brine, dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by flash chromatograpgy on silica gel eluting with 10-30% EtOAc/hexanes. The purified intermediate was added into a mixture solution of THF (8.0 mL), water (30 mL) and hydrogen chloride (30 mL, 100 mmol). The resulting suspension was stirred at room temperature for 2 hours. The mixture was adjusted to pH=9-10 with 6 N NaOH and extracted with EtOAc (2×). The combined extracts were washed with water, brine and dried over anhydrous Na2SO4. After filtration and concentration, the residue was added into a mixture solvents of hexane and EtOAc (9/1, 50 mL). The solid formed was filtered to give 4.2 g (69%) of 4-(1H-pyrazol-4-yl)-5-fluoro-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridine as a light green solid. LC/MS found: 333.2 (M+H)+.

후처리

  1. temperatureAfter being cooled to room temperature
  2. washwashed with water and brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by flash chromatograpgy on silica gel eluting with 10-30% EtOAc/hexanes
  6. stirringThe resulting suspension was stirred at room temperature for 2 hours
  7. extractionextracted with EtOAc (2×)
  8. washThe combined extracts were washed with water, brine
  9. dry with materialdried over anhydrous Na2SO4
  10. filtrationAfter filtration and concentration
  11. additionthe residue was added into a mixture solvents of hexane and EtOAc (9/1, 50 mL)
  12. customThe solid formed
  13. filtrationwas filtered

출처 및 근거

ORD 기록
ord-81f874b09d594f40a4153014975954ef
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08765734B2

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