Sodium Iodide → 2-iodo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(4-cyano-piperidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide

HRID 245966

Reaction equation

HRID 245966 reaction equation
[I-:1].[Na+].[C:3]([CH:5]1[CH2:10][CH2:9][N:8]([C:11](=[O:37])[C@H:12]([NH:16][C:17]([C:19]2[C:27]3[C:22](=[N:23][CH:24]=[C:25](Br)[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])[CH:13]2[CH2:15][CH2:14]2)[CH2:7][CH2:6]1)#[N:4].CN[C@@H]1CCCC[C@H]1NC>[Cu]I.O1CCOCC1>[C:3]([CH:5]1[CH2:10][CH2:9][N:8]([C:11](=[O:37])[C@H:12]([NH:16][C:17]([C:19]2[C:27]3[C:22](=[N:23][CH:24]=[C:25]([I:1])[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])[CH:13]2[CH2:15][CH2:14]2)[CH2:7][CH2:6]1)#[N:4]

Participants

6

Reactant 3

HCID 5238Sodium IodideHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 866578732-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(4-cyano-piperidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide

Product 1

HCID 866779272-iodo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(4-cyano-piperidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amideYield 80%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

In a 5 mL microwave vial were placed copper(I) iodide (5 mg, 0.027 mmol), sodium iodide (120 mg, 0.80 mmol), 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(4-cyano-piperidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide (150 mg, 0.27 mmol), 1,4-dioxane (1 mL) and trans-N,N′-dimethylcyclohexane-1,2-diamine (8 mg, 0.054 mmol). The vial was purged with a stream of nitrogen then sealed and heated in an oil bath at 110° C. for 20 h. The reaction mixture was cooled to room temperature and quenched with sat'd aqueous NH4OH (3 mL) then diluted with water and extracted with CH2Cl2. The organics were dried over MgSO4 and concentrated. The residue was purified by silica gel chromatography with 50% to 80% EtOAc/hexanes to isolate 130 mg (80%) of 2-iodo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(4-cyano-piperidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide as an orange foamy solid.

Workup

  1. customThe vial was purged with a stream of nitrogen
  2. customthen sealed
  3. temperatureThe reaction mixture was cooled to room temperature
  4. customquenched with sat'd aqueous NH4OH (3 mL)
  5. additionthen diluted with water
  6. extractionextracted with CH2Cl2
  7. dry with materialThe organics were dried over MgSO4
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel chromatography with 50% to 80% EtOAc/hexanes

Sources & evidence

ORD record
ord-507d0432198a4b99bf5ad661fb738c13
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Linked notes

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