HCID 57516647, compound → HCID 67385987, compound

HRID 1898624Notes

Reaction equation

HRID 1898624 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].[CH:37]1([CH2:40][N:41]2[CH:45]=[C:44]([Sn](CCCC)(CCCC)CCCC)[N:43]=[CH:42]2)[CH2:39][CH2:38]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:44]4[N:43]=[CH:42][N:41]([CH2:40][CH:37]5[CH2:39][CH2:38]5)[CH:45]=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 57516647HCID 57516647, compoundHCID 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 67385987HCID 67385987, compoundYield 100.7%

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-]pyrazine-7-carboxylic acid [(R)-1-(4-cyano-piperidine-1-carbonyl)-2,2-dimethyl-propyl]-amide (150 mg, 0.26 mmol) and 1-cyclopropylmethyl-4-tributylstannanyl-1H-imidazole (160 mg, 0.39 mmol) were dissolved in DMF (2 mL). Pd(PPh3)4 (15 mg, 0.013 mmol) and CuI (10 mg, 0.052 mmol) were added. The reaction mixture was heated at 80° C. for 1 h then 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 (0-5% MeOH/EtOAc) to afford 162 mg (99%) of 2-(1-cyclopropylmethyl-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 viscous colorless oil.

Workup

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

Sources & evidence

ORD record
ord-f5a6eb42a01b4a988ce125d36cee6991
Source dataset
uspto-grants-2013_08
Patent number
US08518945B2

Reaction notes

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