Pyrazole → 3-(1H-Pyrazol-1-yl)-N-[(1S,2S)-2-{[5-(trifluoromethyl)pyrazin-2-yl]amino}cyclopentyl]pyridine-2-carboxamide

HRID 1750610Notes

Reaction equation

HRID 1750610 reaction equation
Br[C:2]1[C:3]([C:8]([NH:10][C@H:11]2[CH2:15][CH2:14][CH2:13][C@@H:12]2[NH:16][C:17]2[CH:22]=[N:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][N:18]=2)=[O:9])=[N:4][CH:5]=[CH:6][CH:7]=1.[NH:27]1[CH:31]=[CH:30][CH:29]=[N:28]1.C(=O)([O-])[O-].[Cs+].[Cs+].CN[C@@H]1CCCC[C@H]1NC>CN(C=O)C.C(OCC)(=O)C.[Cu]I>[N:27]1([C:2]2[C:3]([C:8]([NH:10][C@H:11]3[CH2:15][CH2:14][CH2:13][C@@H:12]3[NH:16][C:17]3[CH:22]=[N:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][N:18]=3)=[O:9])=[N:4][CH:5]=[CH:6][CH:7]=2)[CH:31]=[CH:30][CH:29]=[N:28]1

Participants

8

Reactant 4

HCID 1048PyrazoleHCID 10796Cesium carbonateHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 1183082783-Bromo-N-[(1S,2S)-2-{[5-(trifluoromethyl)pyrazin-2-yl]amino}cyclopentyl]pyridine-2-carboxamide

Product 1

HCID 1183082403-(1H-Pyrazol-1-yl)-N-[(1S,2S)-2-{[5-(trifluoromethyl)pyrazin-2-yl]amino}cyclopentyl]pyridine-2-carboxamide

Reagents, catalysts & solvents 3

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

Procedure

A solution of 3-bromo-N-[(1S,2S)-2-{[5-(trifluoromethyl)pyrazin-2-yl]amino}cyclopentyl]pyridine-2-carboxamide (Example 28; 100 mg, 0.23 mmol), 1H-pyrazole (CAS number 288-13-1; 32 mg, 0.47 mmol), cesium carbonate (151 mg, 0.47 mmol), copper (I) iodide (2.2 mg, 0.012 mmol) and trans-1-N,2-N-dimethylcyclohexane-1,2-diamine (1.7 mg, 0.012 mmol) in dry DMF (0.8 ml) was subjected to microwave irradiation at 120° C. for 1 hour. The reaction mixture was diluted with ethyl acetate and washed with water (×3) and brine, filtered through a hydrophobic frit and concentrated in vacuo. The resulting residue was purified by reverse phase preparative HPLC (eluted with acetonitrile/water containing 0.1% ammonia) to afford the title compound.

Workup

  1. customirradiation at 120° C. for 1 hour
  2. washwashed with water (×3) and brine
  3. filtrationfiltered through a hydrophobic frit
  4. concentrationconcentrated in vacuo
  5. customThe resulting residue was purified by reverse phase preparative HPLC (eluted with acetonitrile/water containing 0.1% ammonia)

Sources & evidence

ORD record
ord-9a0671d35ecc4d4ab5734f66f14837c1
Source dataset
uspto-grants-2015_10
Patent number
US09156829B2

Reaction notes

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