Cesium carbonate → N-(2-oxo-2-{[(3R)-1-(2-phenyltetrahydro-2H-pyran-4-yl)pyrrolidin-3-yl]amino}ethyl)-3-(trifluoromethyl)benzamide

HRID 564393Notes

Reaction equation

HRID 564393 reaction equation
[O:1]=[C:2]([NH:17][C@@H:18]1[CH2:22][CH2:21][NH:20][CH2:19]1)[CH2:3][NH:4][C:5](=[O:16])[C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([C:12]([F:15])([F:14])[F:13])[CH:7]=1.Br[CH:24]1[CH2:29][CH2:28][O:27][CH:26]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH2:25]1.C(=O)([O-])[O-].[Cs+].[Cs+].C([O-])(O)=O.[Na+]>CN(C=O)C.ClCCl>[O:1]=[C:2]([NH:17][C@@H:18]1[CH2:22][CH2:21][N:20]([CH:24]2[CH2:29][CH2:28][O:27][CH:26]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[CH2:25]2)[CH2:19]1)[CH2:3][NH:4][C:5](=[O:16])[C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([C:12]([F:14])([F:15])[F:13])[CH:7]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 516892Sodium BicarbonateHCID 59556069(R)-N-(2-oxo-2-(pyrrolidin-3-ylamino)ethyl)-3-(trifluoromethyl)benzamideHCID 670050054-bromo-2-phenyltetrahydro-2H-pyran

Product 1

HCID 57814000N-(2-oxo-2-{[(3R)-1-(2-phenyltetrahydro-2H-pyran-4-yl)pyrrolidin-3-yl]amino}ethyl)-3-(trifluoromethyl)benzamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of N-{2-oxo-2-[(3R)-pyrrolidin-3-ylamino]ethyl}-3-(trifluoromethyl)benzamide (100 mg, 0.32 mmol), 4-bromo-2-phenyltetrahydro-2H-pyran (92 mg, 0.38 mmol, prepared according to Org. Let. 2003, 1979-1982) in DMF (3 mL) was added cesium carbonate (156 mg, 0.48 mmol) and the mixture was heated to 60° C. overnight. The mixture was cooled to room temperature, and NaHCO3 (sat. aq., 10 mL) and dichloromethane (10 mL) were added. The organic layer was separated and the aqueous layer was washed with an addition portion of dichloromethane (10 mL). The organic layers were combined, dried over Na2SO4, filtered and concentrated. The resulting crude product was subjected to preparative HPLC to afford, as a mixture of diastereomers, N-(2-oxo-2-{[(3R)-1-(2-phenyltetrahydro-2H-pyran-4-yl)pyrrolidin-3-yl]amino}ethyl)-3-(trifluoromethyl)benzamide as a white solid. 1H-NMR (CDCl3) δ: 1.42-1.71 (m, 2H), 1.93-1.99 (m, 2H), 2.15-2.20 (m, 2H), 2.15-2.20 (m, 1H), 2.59-2.72 (m, 1H), 3.53-3.61 (m, 2H), 3.87-3.99 (m, 2H), 4.09-4.19 (m, 3H), 4.29-4.32 (m, 2H), 7.28-7.33 (m, 5H), 7.55-7.58 (m, 1H), 7.73-7.75 (m, 1H), 8.00-8.03 (m, 1H), 8.08-8.11 (m, 1H). MS m/z: 476 (M+1).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. customThe organic layer was separated
  3. washthe aqueous layer was washed with an addition portion of dichloromethane (10 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-4a21c9def60846c1b5b4b43742de4612
Source dataset
uspto-grants-2011_11
Patent number
US08067457B2

Reaction notes

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