HCID 57516653, compound → HCID 86657875, compound

HRID 1898636Notes

Reaction equation

HRID 1898636 reaction equation
Br[C:2]1[N:3]=[C:4]2[C:10]([CH:11]=[O:12])=[CH:9][N:8]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[C:5]2=[N:6][CH:7]=1.[F:21][C:22]1[CH:27]=[CH:26][C:25]([F:28])=[CH:24][C:23]=1[N:29]1[CH:33]=[C:32]([Sn](CCCC)(CCCC)CCCC)[N:31]=[CH:30]1>CN(C=O)C.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.[Cu]I>[F:21][C:22]1[CH:27]=[CH:26][C:25]([F:28])=[CH:24][C:23]=1[N:29]1[CH:33]=[C:32]([C:2]2[N:3]=[C:4]3[C:10]([CH:11]=[O:12])=[CH:9][N:8]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[C:5]3=[N:6][CH:7]=2)[N:31]=[CH:30]1

Participants

6

Reactant 2

HCID 57516653HCID 57516653, compoundHCID 578296122-bromo-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde

Product 1

HCID 86657875HCID 86657875, compoundYield 62%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A pressure tube was charged with 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde (0.110 g, 0.31 mmol), Pd(PPh3)4 (0.020 g, 0.017 mmol), CuI (0.012 g, 0.063 mmol) and the above-prepared crude 1-(2,5-difluorophenyl)-4-(tributylstannyl)-1H-imidazole (0.198 g) in 3 mL of DMF. The tube was capped under Ar and the orange yellow mixture stirred at 80° C. for 1.5 h, then allowed to cool. The mixture was partitioned between 20 mL of ethyl acetate and 20 mL of water+20 mL of a sat. aq. NH4Cl solution. The organic layer was washed with 20 mL of a sat. aq. NaCl solution, dried over Na2SO4, filtered and concentrated. Column chromatography (20-100% EtOAc/hexanes) of the residue afforded 0.087 g (62%) of 2-[1-(2,5-difluoro-phenyl)-1H-imidazol-4-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde as a slightly impure yellow oil, which was used without further purification. MS: (M+Na)+=478.

Workup

  1. customThe tube was capped under Ar
  2. temperatureto cool
  3. customThe mixture was partitioned between 20 mL of ethyl acetate and 20 mL of water+20 mL of a sat. aq. NH4Cl solution
  4. washThe organic layer was washed with 20 mL of a sat. aq. NaCl solution
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-352115bb86024cf1a6a13d6264dca80a
Source dataset
uspto-grants-2013_08
Patent number
US08518945B2

Reaction notes

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