3-Bromo-4-(4,4-difluorocyclohexyl)-1,1,1-trifluorobutan-2-one → Methyl 3-(4,4-difluorocyclohexylmethyl)-6-methoxy-2-(trifluoromethyl)imidazo[1,2-a]pyridine-7-carboxylate

HRID 1468293Notes

Reaction equation

HRID 1468293 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:9]([O:12][CH3:13])=[CH:10][N:11]=1)[C:5]([O:7][CH3:8])=[O:6].Br[CH:15]([CH2:22][CH:23]1[CH2:28][CH2:27][C:26]([F:30])([F:29])[CH2:25][CH2:24]1)[C:16](=O)[C:17]([F:20])([F:19])[F:18]>C(O)CCC>[F:29][C:26]1([F:30])[CH2:27][CH2:28][CH:23]([CH2:22][C:15]2[N:11]3[CH:10]=[C:9]([O:12][CH3:13])[C:4]([C:5]([O:7][CH3:8])=[O:6])=[CH:3][C:2]3=[N:1][C:16]=2[C:17]([F:18])([F:19])[F:20])[CH2:24][CH2:25]1

Participants

4

Reactant 2

HCID 867100943-Bromo-4-(4,4-difluorocyclohexyl)-1,1,1-trifluorobutan-2-oneHCID 86710107Methyl 2-amino-5-methoxyisonicotinate

Product 1

HCID 86710108Methyl 3-(4,4-difluorocyclohexylmethyl)-6-methoxy-2-(trifluoromethyl)imidazo[1,2-a]pyridine-7-carboxylateYield 52%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
130 °C

Procedure

Methyl 2-amino-5-methoxyisonicotinate (20 mg, 0.110 mmol) obtained in step 3 was suspended in n-butanol (1.10 mL), and the suspension was stirred overnight at 130° C. after adding 3-bromo-4-(4,4-difluorocyclohexyl)-1,1,1-trifluorobutan-2-one (53 mg, 0.165 mmol) obtained in step 2 of Example 36, and molecular sieve 4A (20 mg). The reaction mixture was allowed to cool to room temperature, filtered through Celite (registered trademark) after adding a sodium hydrogen carbonate aqueous solution, and extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and dried over anhydrous sodium sulfate. The solvent was then evaporated under reduced pressure. The residue was purified by preparative thin-layer chromatography (chloroform/methanol=15/1) to give methyl 3-(4,4-difluorocyclohexylmethyl)-6-methoxy-2-(trifluoromethyl)imidazo[1,2-a]pyridine-7-carboxylate (23.0 mg, yield 52%).

Workup

  1. temperatureto cool to room temperature
  2. filtrationfiltered through Celite (registered trademark)
  3. additionafter adding a sodium hydrogen carbonate aqueous solution
  4. extractionextracted with ethyl acetate
  5. washThe organic layer was washed with water and saturated brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. customThe solvent was then evaporated under reduced pressure
  8. customThe residue was purified by preparative thin-layer chromatography (chloroform/methanol=15/1)

Sources & evidence

ORD record
ord-a5c2aac7efd149d48f7d4f0e6614ebf0
Source dataset
uspto-grants-2015_04
Patent number
US09000186B2

Reaction notes

Loading…