Potassium Iodide → 8-[(2,6-Difluorobenzyl)oxy]-2,6-dimethyl-N-{2-methyl-2-[(2,2,2-trifluoroethyl)amino]propyl}-imidazo[1,2-a]pyridine-3-carboxamide

HRID 2275887Notes

Reaction equation

HRID 2275887 reaction equation
[NH2:1][C:2]([CH3:29])([CH3:28])[CH2:3][NH:4][C:5]([C:7]1[N:11]2[CH:12]=[C:13]([CH3:26])[CH:14]=[C:15]([O:16][CH2:17][C:18]3[C:23]([F:24])=[CH:22][CH:21]=[CH:20][C:19]=3[F:25])[C:10]2=[N:9][C:8]=1[CH3:27])=[O:6].ClC(Cl)(Cl)S(O[CH2:36][C:37]([F:40])([F:39])[F:38])(=O)=O.C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>CN(C=O)C.O>[F:24][C:23]1[CH:22]=[CH:21][CH:20]=[C:19]([F:25])[C:18]=1[CH2:17][O:16][C:15]1[C:10]2[N:11]([C:7]([C:5]([NH:4][CH2:3][C:2]([CH3:29])([NH:1][CH2:36][C:37]([F:40])([F:39])[F:38])[CH3:28])=[O:6])=[C:8]([CH3:27])[N:9]=2)[CH:12]=[C:13]([CH3:26])[CH:14]=1

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 900272,2,2-Trifluoroethyl trichloromethanesulphonate3×HCID 86717963N-(2-Amino-2-methylpropyl)-8-[(2,6-difluorobenzyl)oxy]-2,6-dimethylimidazo[1,2-a]pyridine-3-carboxamide

Product 1

HCID 867179658-[(2,6-Difluorobenzyl)oxy]-2,6-dimethyl-N-{2-methyl-2-[(2,2,2-trifluoroethyl)amino]propyl}-imidazo[1,2-a]pyridine-3-carboxamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

100 mg (0.25 mmol) of N-(2-amino-2-methylpropyl)-8-[(2,6-difluorobenzyl)oxy]-2,6-dimethylimidazo[1,2-a]pyridine-3-carboxamide (Example 74) were initially charged in 2 ml of DMF, 0.041 ml (0.25 mmol) of 2,2,2-trifluoroethyl trichloromethanesulphonate, 69 mg (0.50 mmol) of potassium carbonate and 4.1 mg (0.025 mmol) of potassium iodide were added and the mixture was then stirred at RT overnight. 0.082 ml (0.50 mmol) of 2,2,2-trifluoroethyl trichloromethanesulphonate was then added, and the mixture was once more stirred at RT overnight. Another 0.123 ml (0.75 mmol) of 2,2,2-trifluoroethyl trichloromethanesulphonate were added, and the mixture was once more stirred at RT overnight. For work-up, 1 ml of water was added, the mixture was filtered through an Extrelut cartridge, eluted with dichloromethane, and the filtrate was concentrated. The crude product was purified by preparative HPLC (RP18 column, mobile phase: acetonitrile/water gradient with addition of 0.5% ammonium hydroxide). The product fractions were combined, evaporated and dried under high vacuum.

Workup

  1. stirringthe mixture was once more stirred at RT overnight
  2. stirringthe mixture was once more stirred at RT overnight
  3. filtrationthe mixture was filtered through an Extrelut cartridge
  4. washeluted with dichloromethane
  5. concentrationthe filtrate was concentrated
  6. customThe crude product was purified by preparative HPLC (RP18 column, mobile phase: acetonitrile/water gradient with addition of 0.5% ammonium hydroxide)
  7. customevaporated
  8. customdried under high vacuum

Sources & evidence

ORD record
ord-7548586839734bfe97a0e66a0c7b9f72
Source dataset
uspto-grants-2015_09
Patent number
US09126998B2

Reaction notes

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