Potassium Acetate → 2-[2-Fluoro-4-(7-pyridin-4-yl-imidazo[1,2-a]pyridin-3-yl)-phenyl]-N-(5-isopropyl-4-methyl-thiazol-2-yl)-acetamide

HRID 1446764Notes

Reaction equation

HRID 1446764 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([C:7]2[CH:12]=[CH:11][N:10]3[CH:13]=[CH:14][N:15]=[C:9]3[CH:8]=2)=[CH:3][CH:2]=1.Br[C:17]1[CH:22]=[CH:21][C:20]([CH2:23][C:24]([NH:26][C:27]2[S:28][C:29]([CH:33]([CH3:35])[CH3:34])=[C:30]([CH3:32])[N:31]=2)=[O:25])=[C:19]([F:36])[CH:18]=1.C([O-])(=O)C.[K+]>CS(C)=O>[F:36][C:19]1[CH:18]=[C:17]([C:13]2[N:10]3[CH:11]=[CH:12][C:7]([C:4]4[CH:3]=[CH:2][N:1]=[CH:6][CH:5]=4)=[CH:8][C:9]3=[N:15][CH:14]=2)[CH:22]=[CH:21][C:20]=1[CH2:23][C:24]([NH:26][C:27]1[S:28][C:29]([CH:33]([CH3:35])[CH3:34])=[C:30]([CH3:32])[N:31]=1)=[O:25]

Participants

5

Reactant 3

HCID 517044Potassium AcetateHCID 685456367-Pyridin-4-yl-imidazo[1,2-a]pyridineHCID 866343102-(4-Bromo-2-fluoro-phenyl)-N-(5-isopropyl-4-methyl-thiazol-2-yl)-acetamide

Product 1

HCID 118534672-[2-Fluoro-4-(7-pyridin-4-yl-imidazo[1,2-a]pyridin-3-yl)-phenyl]-N-(5-isopropyl-4-methyl-thiazol-2-yl)-acetamideYield 11.3%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

Combine 7-pyridin-4-yl-imidazo[1,2-a]pyridine (0.242 g, 1.24 mmol), 2-(4-Bromo-2-fluoro-phenyl)-N-(5-isopropyl-4-methyl-thiazol-2-yl)-acetamide (0.460 g, 1.24 mmol), and potassium acetate (0.243 g, 2.48 mmol) in DMSO (5 mL). De-gas the mixture with N2 for 10 minutes, then add dichlorobis(triphenylphosphine) palladium(II) (0.087 g, 0.124 mmol). Stir the reaction at 100° C. under N2 for 14 hours. Purify using an SCX cartridge (10 g VARIAN bond elut), eluting with 1:1 methanol:dichloromethane, then 1:1 2 M NH3 in methanol:dichloromethane. The latter is purified via reverse phase chromatography using a 25 cm by 50.8 mm (i.d.) column w/10 micron particles (MeCN/0.03% HCl H2O (5:95) to 100% MeCN; 30 minutes). Compound obtained is extracted with ethyl acetate versus 1 N NaOH. The organic layer is washed with aqueous saturated sodium chloride. Dry the resulting organics over magnesium sulfate, filter, and concentrate to afford product (0.068 g, 11%). MS(ES), m/z 486 (M+1).

Workup

  1. customDe-gas the mixture with N2 for 10 minutes
  2. customthe reaction at 100° C. under N2 for 14 hours
  3. customPurify
  4. washeluting with 1:1 methanol
  5. customThe latter is purified via reverse phase chromatography
  6. customby 50.8 mm (i.d.) column w/10 micron particles (MeCN/0.03% HCl H2O (5:95) to 100% MeCN; 30 minutes)
  7. customCompound obtained
  8. extractionis extracted with ethyl acetate versus 1 N NaOH
  9. washThe organic layer is washed with aqueous saturated sodium chloride
  10. dry with materialDry the resulting organics over magnesium sulfate
  11. filtrationfilter
  12. concentrationconcentrate

Sources & evidence

ORD record
ord-85665301d9884b379753a58497ad4dbb
Source dataset
uspto-grants-2010_02
Patent number
US07666879B2

Reaction notes

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