Potassium Carbonate → 5-bromo-3-methyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridine

HRID 538434Notes

Reaction equation

HRID 538434 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:10](I)=[CH:9][N:8]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[C:5]2=[N:6][CH:7]=1.[CH3:20]B1OB(C)OB(C)O1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.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>[Br:1][C:2]1[CH:3]=[C:4]2[C:10]([CH3:20])=[CH:9][N:8]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[C:5]2=[N:6][CH:7]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 574072TrimethylboroxineHCID 592970265-bromo-3-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 665911515-bromo-3-methyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridineYield 2.9%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 5-bromo-3-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridine (1.05 g, 2.33 mmol), 2,4,6-trimethyl-1,3,5,2,4,6-trioxatriborinane (2.6 mL, 18.6 mmol), and potassium carbonate (0.97 g, 7.0 mmol) in 10% aqueous dioxane (19 mL) was sparged with Ar. Pd(PPh3)4 (134 mg, 0.12 mmol) was added and the reaction was sealed and heated to 90° C. for 6.5 h. The reaction was allowed to cool to rt and concentrated in vacuo. The remaining residue was dissolved in EtOAc (250 mL), washed sequentially with water (100 mL), aqueous 0.1 M HCl solution (150 mL), and brine (100 mL). The resulting solution was dried (Na2SO4) and concentrated. Purification by reverse phase HPLC yielded 23 mg of 5-bromo-3-methyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridine as the TFA salt: LCMS (m/z): 342.9 (MH+), tR=0.74 min

Workup

  1. customwas sparged with Ar
  2. customthe reaction was sealed
  3. temperatureto cool to rt
  4. concentrationconcentrated in vacuo
  5. dissolutionThe remaining residue was dissolved in EtOAc (250 mL)
  6. washwashed sequentially with water (100 mL), aqueous 0.1 M HCl solution (150 mL), and brine (100 mL)
  7. dry with materialThe resulting solution was dried (Na2SO4)
  8. concentrationconcentrated
  9. customPurification by reverse phase HPLC

Sources & evidence

ORD record
ord-16fbd766508141f5b988812ba4d8e0e1
Source dataset
uspto-grants-2014_10
Patent number
US08865732B2

Reaction notes

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