Cesium carbonate → benzyl ((1S,3R)-3-(pyrazin-2-ylamino)cyclohexyl)carbamate

HRID 75051

Reaction equation

HRID 75051 reaction equation
[NH2:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][C@H:4]([NH:8][C:9](=[O:18])[O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:3]1.C(=O)([O-])[O-].[Cs+].[Cs+].I[C:26]1[CH:31]=[N:30][CH:29]=[CH:28][N:27]=1.CC(C)C(C1CCCCC1=O)=O.C(=O)(O)[O-].[Na+]>CN(C=O)C.[Cu]I.C(OCC)(=O)C>[N:27]1[CH:28]=[CH:29][N:30]=[CH:31][C:26]=1[NH:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][C@H:4]([NH:8][C:9](=[O:18])[O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:3]1

Participants

9

Reactant 5

HCID 10796Cesium carbonateHCID 516892Sodium BicarbonateHCID 642841IodopyrazineHCID 114693012-(2-Methylpropanoyl)cyclohexan-1-oneHCID 69756715Benzyl ((1S,3R)-3-aminocyclohexyl)carbamate2×

Product 1

HCID 68007319benzyl ((1S,3R)-3-(pyrazin-2-ylamino)cyclohexyl)carbamate

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A suspension of CuI (0.006 g, 0.030 mmol), benzyl N-[(1S,3R)-3-aminocyclo-hexyl]carbamate, 18e, (0.075 g, 0.302 mmol) and cesium carbonate (0.197 g, 0.604 mmol) in DMF was evacuated and refilled with nitrogen multiple times. 2-iodopyrazine (0.036 mL, 0.362 mmol) and 2-(2-methylpropanoyl)cyclohexanone (0.020 mL g, 0.121 mmol) were then added and the reaction was stirred at room temperature overnight. The reaction was diluted into ethyl acetate and aqueous saturated sodium bicarbonate. The organic phase was separated, dried (MgSO4), filtered and concentrated in vacuo. The crude residue was purified by silica gel chromatography (0-10% MeOH/CH2Cl2) to afford 40 mg of the desired product as yellow solid.

Workup

  1. customwas evacuated
  2. additionrefilled with nitrogen multiple times
  3. customThe organic phase was separated
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude residue was purified by silica gel chromatography (0-10% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-9b84f14b8bf940c9bf556156b1b98b6d
Source dataset
uspto-grants-2014_09
Patent number
US08829007B2

Linked notes

Loading…