2-Fluoropyridine → 2-(1,1'-biphenyl-4-yl)-N-{(1R)-1-[5-(pyridine-2-yloxy)pyridine-2-yl]ethyl}acetamide

HRID 2383525Notes

Reaction equation

HRID 2383525 reaction equation
[C:1]1([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:6]=[CH:5][C:4]([CH2:7][C:8]([NH:10][C@@H:11]([C:13]2[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][N:14]=2)[CH3:12])=[O:9])=[CH:3][CH:2]=1.F[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[C:1]1([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:2]=[CH:3][C:4]([CH2:7][C:8]([NH:10][C@@H:11]([C:13]2[CH:18]=[CH:17][C:16]([O:19][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=3)=[CH:15][N:14]=2)[CH3:12])=[O:9])=[CH:5][CH:6]=1

Participants

5

Reactant 3

HCID 97462-Fluoropyridine2×HCID 10796Cesium carbonateHCID 247655732-(1,1'-biphenyl-4-yl)-N-[(1R)-1-(5-hydroxypyridin-2-yl)ethyl]acetamide

Product 1

HCID 247655712-(1,1'-biphenyl-4-yl)-N-{(1R)-1-[5-(pyridine-2-yloxy)pyridine-2-yl]ethyl}acetamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
130 °C

Procedure

To a mixture of 2-(1,1′-biphenyl-4-yl)-N-[(1R)-1-(5-hydroxypyridin-2-yl)ethyl]acetamide (40 mg, 0.12 mmol) and 2-fluoropyridine (31 μL, 0.36 mmol) in DMF (3.0 ml) was added cesium carbonate (137 mg, 0.42 mmol). The reaction was heated to 130° C. for 30 minutes. An additional amount of 2-fluoropyridine (31 μL, 0.36 mmol) was added and the mixture heated for one hour at 130° C. The reaction was cooled, washed with brine and extracted with EtOAc. The organic layer was dried over Na2SO4, filtered and concentrated in vacuo to give an oil. Reverse phase prep HPLC chromatography afforded the mono-trifluoroacetate salt of 2-(1,1′-biphenyl-4-yl)-N-{(1R)-1-[5-(pyridine-2-yloxy)pyridine-2-yl]ethyl}acetamide as a yellow oil. 1H NMR (CD3OD, 400 MHz) δ 8.61 (s, 1H; 8.11 (dd, J=1.60 and 4.80 Hz, 1H); 8.01 (dd, J=2.80 and 8.80 Hz, 1H); 7.89 (m, 1H); 7.71 (d, J=8.80 Hz, 1H); 7.56 (m, 4H); 7.38 (m, 5H); 7.18 (m, 1H); 7.12 (d, J=8.40 Hz, 1H); 5.12 (m, 1H), 3.63 (s, 2H), 1.58 (d, J=7.20 Hz, 3H). HRMS (ES) exact mass calcd for C26H23N3O2: 410.1863, Found: 410.1873.

Workup

  1. temperaturethe mixture heated for one hour at 130° C
  2. temperatureThe reaction was cooled
  3. washwashed with brine
  4. extractionextracted with EtOAc
  5. dry with materialThe organic layer was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto give an oil

Sources & evidence

ORD record
ord-bd47c74cebba4634bd2b99ccf0e506fe
Source dataset
uspto-grants-2012_09
Patent number
US08263627B2

Reaction notes

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