Cesium carbonate → N-Benzyl-4-methyl-2-(2-oxo-4-((5-phenyl-1,3,4-oxadiazol-2-yl)methoxy)pyridin-1(2H)-yl)thiazole-5-carboxamide

HRID 1887337

Reaction equation

HRID 1887337 reaction equation
[CH2:1]([NH:8][C:9]([C:11]1[S:15][C:14]([N:16]2[CH:21]=[CH:20][C:19]([OH:22])=[CH:18][C:17]2=[O:23])=[N:13][C:12]=1[CH3:24])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl[CH2:32][C:33]1[O:34][C:35]([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)=[N:36][N:37]=1>CN(C)C=O>[CH2:1]([NH:8][C:9]([C:11]1[S:15][C:14]([N:16]2[CH:21]=[CH:20][C:19]([O:22][CH2:32][C:33]3[O:34][C:35]([C:38]4[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=4)=[N:36][N:37]=3)=[CH:18][C:17]2=[O:23])=[N:13][C:12]=1[CH3:24])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 3149412-(Chloromethyl)-5-phenyl-1,3,4-oxadiazoleHCID 54742338N-benzyl-2-(4-hydroxy-2-oxopyridin-1(2H)-yl)-4-methylthiazole-5-carboxamide

Product 1

HCID 57744445N-Benzyl-4-methyl-2-(2-oxo-4-((5-phenyl-1,3,4-oxadiazol-2-yl)methoxy)pyridin-1(2H)-yl)thiazole-5-carboxamideYield 38%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of N-benzyl-2-(4-hydroxy-2-oxopyridin-1(2H)-yl)-4-methylthiazole-5-carboxamide (0.20 g, 0.58 mmol) in anhydrous N,N-dimethylformamide (8 mL) was added cesium carbonate (0.32 g, 0.99 mmol) and catalytic amount of n-tetrabutylammonium iodide, followed by the addition of 2-(chloromethyl)-5-phenyl-1,3,4-oxadiazole (0.15 g, 0.76 mmol). The reaction mixture was heated at 80° C. for 20 hours and concentrated in vacuo, followed by the addition of dichloromethane (100 mL). The mixture was washed with water (70 mL). The organic layer was dried over anhydrous sodium sulfate and filtered. The solvent was concentrated in vacuo. The residue was recrystallized in ethyl acetate and hexane. The solid was collected by filtration and washed with methanol and hexanes to afford the title compound as a colorless solid in 38% yield (0.11 g): 1H NMR (300 MHz, DMSO-d6) δ 8.84 (t, J=5.9 Hz, 1H), 8.69 (d, J=8.0 Hz, 1H), 8.04-8.01 (m, 2H), 7.69-7.57 (m, 3H), 7.37-7.29 (m, 4H), 7.27-7.21 (m, 1H), 6.50-6.43 (m, 2H), 5.64 (s, 2H), 4.42 (d, J=5.9 Hz, 2H), 2.58 (s, 3H); MS (ES+) m/z 500.2 (M+1), 522.2 (M+23).

Workup

  1. concentrationconcentrated in vacuo
  2. additionfollowed by the addition of dichloromethane (100 mL)
  3. washThe mixture was washed with water (70 mL)
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationThe solvent was concentrated in vacuo
  7. customThe residue was recrystallized in ethyl acetate
  8. filtrationThe solid was collected by filtration
  9. washwashed with methanol and hexanes

Sources & evidence

ORD record
ord-28165492c80c4f76ad3ebbb1b5850879
Source dataset
uspto-grants-2013_08
Patent number
US08501746B2

Linked notes

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