Cesium carbonate → HCID 68161654, compound

HRID 2400350Notes

Reaction equation

HRID 2400350 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][N:5]2[C:8]([C:11]3[CH:12]=[C:13]([NH:17][C:18]([NH:20][CH2:21][C:22]([F:25])([F:24])[F:23])=[O:19])[CH:14]=[CH:15][CH:16]=3)=[CH:9][N:10]=[C:4]2[CH:3]=1.[C:26]([C:28]1[N:32]([CH3:33])[CH:31]=[N:30][CH:29]=1)#[CH:27].C(=O)([O-])[O-].[Cs+].[Cs+]>CS(C)=O>[ClH:1].[ClH:1].[CH3:33][N:32]1[C:28]([C:26]#[C:27][C:2]2[CH:7]=[CH:6][N:5]3[C:8]([C:11]4[CH:12]=[C:13]([NH:17][C:18]([NH:20][CH2:21][C:22]([F:25])([F:24])[F:23])=[O:19])[CH:14]=[CH:15][CH:16]=4)=[CH:9][N:10]=[C:4]3[CH:3]=2)=[CH:29][N:30]=[CH:31]1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 33331065-Ethynyl-1-methyl-1H-imidazoleHCID 574976981-(3-(7-Chloroimidazo[1,2-a]pyridin-3-yl)phenyl)-3-(2,2,2-trifluoroethyl)urea

Product 1

HCID 68161654HCID 68161654, compoundYield 63.1%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 1-[3-(7-Chloro-imidazo[1,2-a]pyridin-3-yl)-phenyl]-3-(2,2,2-trifluoro-ethyl)-urea (3.08 g, 8.3 mmol), 5-Ethynyl-1-methyl-1H-imidazole (1.78 g, 10 mmol) and cesium carbonate (5.43 g, 16.7 mmol) in dry DMSO (31 ml) was deoxygenated by evacuation /refill with N2 (×3). PdCl2(PCy3)2 (185 mg, 0.25 mmol) was added and the mixture was deoxygenated again (×3) then stirred and heated at 100° C. under N2 for 16 hours. The reaction was allowed to cool to RT, diluted with water (65 ml) and the mixture was extracted with EtOAc (3×50 ml). The combined organic extracts were washed with brine (40 ml) then dried (MgSO4), filtered and evaporated. The residue was mixed with dichloromethane (20 ml), cooled in ice and filtered to give the title compound (1.34 g, yellow solid). 1H NMR (400 MHz, Me-d3-OD): 8.59 (1H, d), 7.87-7.74 (4H, m), 7.50 (1H, t), 7.42 (1H, d), 7.37 (1H, s), 7.32 (1H, d), 7.10 (1H, dd), 3.95 (2H, q), 3.85 (3H, s). A solution of the title compound in methanol (10 ml) was cooled in ice and was treated with a solution of saturated hydrogen chloride in ethyl acetate (15 ml). The mixture was evaporated to give the bis-HCl salt (1.59 g, yellow foam). 1H NMR (400 MHz, Me-d3-OD): 9.06 (1H, s), 8.88 (1H, d), 8.34-8.27 (2H, m), 8.08 (2H, d), 7.65 (1H, d), 7.59 (1H, t), 7.47-7.35 (2H, m), 4.09 (3H, s), 3.96 (2H, q).

Workup

  1. customwas deoxygenated by evacuation /refill with N2 (×3)
  2. customthe mixture was deoxygenated again (×3)
  3. temperatureto cool to RT
  4. additiondiluted with water (65 ml)
  5. extractionthe mixture was extracted with EtOAc (3×50 ml)
  6. washThe combined organic extracts were washed with brine (40 ml)
  7. dry with materialthen dried (MgSO4)
  8. filtrationfiltered
  9. customevaporated
  10. additionThe residue was mixed with dichloromethane (20 ml)
  11. temperaturecooled in ice
  12. filtrationfiltered

Sources & evidence

ORD record
ord-1c93203456374cf2b5e32651de569f90
Source dataset
uspto-grants-2014_08
Patent number
US08796244B2

Reaction notes

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