1-Methyl-4-(tributylstannyl)-1H-imidazole → 2-(1-methyl-1H-imidazol-4-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(4-cyano-piperidine-1-carbonyl)-2,2-dimethyl-propyl]-amide

HRID 1898539Notes

Reaction equation

HRID 1898539 reaction equation
[C:1]([CH:3]1[CH2:8][CH2:7][N:6]([C:9]([C@H:11]([NH:16][C:17]([C:19]2[C:27]3[N:26]=[C:25](Br)[CH:24]=[N:23][C:22]=3[N:21]([CH2:29][O:30][CH2:31][CH2:32][Si:33]([CH3:36])([CH3:35])[CH3:34])[CH:20]=2)=[O:18])[C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1)#[N:2].[CH3:37][N:38]1[CH:42]=[C:41]([Sn](CCCC)(CCCC)CCCC)[N:40]=[CH:39]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>[C:1]([CH:3]1[CH2:8][CH2:7][N:6]([C:9]([C@H:11]([NH:16][C:17]([C:19]2[C:27]3[C:22](=[N:23][CH:24]=[C:25]([C:41]4[N:40]=[CH:39][N:38]([CH3:37])[CH:42]=4)[N:26]=3)[N:21]([CH2:29][O:30][CH2:31][CH2:32][Si:33]([CH3:36])([CH3:35])[CH3:34])[CH:20]=2)=[O:18])[C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1)#[N:2]

Participants

6

Reactant 2

HCID 219011411-Methyl-4-(tributylstannyl)-1H-imidazoleHCID 584385322-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-]pyrazine-7-carboxylic acid [(R)-1-(4-cyano-piperidine-1-carbonyl)-2,2-dimethyl-propyl]-amide

Product 1

HCID 673864602-(1-methyl-1H-imidazol-4-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(4-cyano-piperidine-1-carbonyl)-2,2-dimethyl-propyl]-amideYield 95%

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 pressure tube 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-]pyrazine-7-carboxylic acid [(R)-1-(4-cyano-piperidine-1-carbonyl)-2,2-dimethyl-propyl]-amide (125 mg, 0.22 mmol) and 1-methyl-4-tributylstannanyl-1H-imidazole (97 mg, 0.26 mmol) were dissolved in DMF (2 mL). Pd(PPh3)4 (12.5 mg, 0.01 mmol) and CuI (8 mg, 0.04 mmol) were added. The tube was sealed and heated at 80° C. for 1.5 h. The reaction mixture was cooled to room temperature, quenched with H2O and extracted with EtOAc. The organic extracts were washed with saturated aqueous LiCl and brine, dried over MgSO4, and concentrated. The residue was purified by SiO2 chromatography (0-10% MeOH/EtOAc) to afford 121 mg (95%) of 2-(1-methyl-1H-imidazol-4-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(4-cyano-piperidine-1-carbonyl)-2,2-dimethyl-propyl]-amide as a light brown gum.

Workup

  1. customThe tube was sealed
  2. temperatureThe reaction mixture was cooled to room temperature
  3. customquenched with H2O
  4. extractionextracted with EtOAc
  5. washThe organic extracts were washed with saturated aqueous LiCl and brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. customThe residue was purified by SiO2 chromatography (0-10% MeOH/EtOAc)

Sources & evidence

ORD record
ord-5491ab969cd4410582a6214be8a4d37f
Source dataset
uspto-grants-2013_08
Patent number
US08518945B2

Reaction notes

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