6-Fluoro-1-tributylstannyl-imidazo[1,5-a]pyridine → 2-(6-fluoro-imidazo[1,5-a]pyridin-1-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-oxazol-2-yl-ethyl)-amide

HRID 245921Notes

Reaction equation

HRID 245921 reaction equation
[O:1]1[CH:5]=[CH:4][N:3]=[C:2]1[C@H:6]([NH:8][C:9]([C:11]1[C:19]2[C:14](=[N:15][CH:16]=[C:17](Br)[N:18]=2)[N:13]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[CH:12]=1)=[O:10])[CH3:7].[F:29][C:30]1[CH:31]=[CH:32][C:33]2[N:34]([CH:36]=[N:37][C:38]=2[Sn](CCCC)(CCCC)CCCC)[CH:35]=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>[O:1]1[CH:5]=[CH:4][N:3]=[C:2]1[C@H:6]([NH:8][C:9]([C:11]1[C:19]2[C:14](=[N:15][CH:16]=[C:17]([C:38]3[N:37]=[CH:36][N:34]4[CH:35]=[C:30]([F:29])[CH:31]=[CH:32][C:33]=34)[N:18]=2)[N:13]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[CH:12]=1)=[O:10])[CH3:7]

Participants

6

Reactant 2

HCID 712799216-Fluoro-1-tributylstannyl-imidazo[1,5-a]pyridineHCID 866779222-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-oxazol-2-yl-ethyl)-amide

Product 1

HCID 712881952-(6-fluoro-imidazo[1,5-a]pyridin-1-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-oxazol-2-yl-ethyl)-amideYield 66%

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

In a round-bottomed flask, 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-oxazol-2-yl-ethyl)-amide (148 mg, 0.32 mmol) and 6-Fluoro-1-tributylstannyl-imidazo[1,5-a]pyridine (380 mg, 0.45 mmol) were dissolved in DMF (3 ml). The flask was evacuated and backfilled with argon then tetrakis(triphenylphosphine)palladium (0) (19 mg, 0.016 mmol) and copper (I) iodide (13 mg, 0.068 mmol) were added. The reaction mixture was stirred at 80° C. in an oil bath overnight then cooled to room temperature, quenched with water and extracted with diethyl ether (2×). The combined organic layers were washed twice with water and once with brine then dried over sodium sulfate, filtered and concentrated. The residue was chromatographed over silica sel with MeOH/CH2Cl2/0.5% NH4OH (gradient 0-2% MeOH) to afford 109 mg (66%) of 2-(6-fluoro-imidazo[1,5-a]pyridin-1-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-oxazol-2-yl-ethyl)-amide as a yellow solid.

Workup

  1. customThe flask was evacuated
  2. temperaturethen cooled to room temperature
  3. customquenched with water
  4. extractionextracted with diethyl ether (2×)
  5. washThe combined organic layers were washed twice with water and once with brine
  6. dry with materialthen dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was chromatographed over silica sel with MeOH/CH2Cl2/0.5% NH4OH (gradient 0-2% MeOH)

Sources & evidence

ORD record
ord-9378917c292d47218e1c432aa861ae30
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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