Hydrochloric Acid → 4-(1H-Pyrazol-4-yl)-1-[2-(trimethylsilyl)ethoxy]methyl-1H-pyrrolo[2,3-b]pyridine

HRID 1617368Notes

Reaction equation

HRID 1617368 reaction equation
Br[C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[CH:9]=[CH:10][C:3]=12.C(OC([N:24]1[CH:28]=[C:27](B2OC(C)(C)C(C)(C)O2)[CH:26]=[N:25]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>[NH:24]1[CH:28]=[C:27]([C:2]2[CH:7]=[CH:6][N:5]=[C:4]3[N:8]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[CH:9]=[CH:10][C:3]=23)[CH:26]=[N:25]1

Participants

10

Reactant 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 574775614-bromo-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 574775784-(1H-Pyrazol-4-yl)-1-[2-(trimethylsilyl)ethoxy]methyl-1H-pyrrolo[2,3-b]pyridineYield 85.5%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 4-bromo-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridine (15.70 g, 47.97 mmol), 1-(1-ethoxyethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (14.04 g, 52.77 mmol), tetrakis(triphenylphosphine)palladium(0) (2.772 g, 2.398 mmol) and sodium carbonate (15.25 g, 143.9 mmol) in 1,4-dioxane (150 mL) and water (75 mL) was stirred at 110° C. for 1 hour. After being cooled to room temperature, the mixture was diluted with EtOAc, and washed with water and brine, dried over Na2SO4 and concentrated. The residue was purified by flash chromatograpgy on silica gel eluting with 10-30% EtOAc/hexanes. The purified intermediate was dissolved in THF (21 mL), water (90 mL) and hydrogen chloride (75 mL, 240 mmol). The resulting suspension was stirred at room temperature for 2 hours. The mixture was adjusted to pH=9-10 with 6 N NaOH. Hexanes (150 mL) were added. The solids formed was filtered and washed with water (3×) to provide 12.9 g (85%) of 4-(1H-pyrazol-4-yl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridine as a white solid. LC/MS found: 315.2 (M+H)+.

Workup

  1. temperatureAfter being cooled to room temperature
  2. washwashed with water and brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customThe residue was purified by flash chromatograpgy on silica gel eluting with 10-30% EtOAc/hexanes
  6. dissolutionThe purified intermediate was dissolved in THF (21 mL)
  7. stirringThe resulting suspension was stirred at room temperature for 2 hours
  8. customThe solids formed
  9. filtrationwas filtered
  10. washwashed with water (3×)

Sources & evidence

ORD record
ord-20a4ddf720a94e9bbf02351e02c97b77
Source dataset
uspto-grants-2014_07
Patent number
US08765734B2

Reaction notes

Loading…