3,5-Difluoropyridin-2-amine → {1-[4-(6,8-Difluoro-3-phenyl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester

HRID 872305Notes

Reaction equation

HRID 872305 reaction equation
[C:1]([O:5][C:6](=[O:28])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18](=O)[CH:19](Br)[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[F:29][C:30]1[C:31]([NH2:37])=[N:32][CH:33]=[C:34]([F:36])[CH:35]=1>C(O)C>[C:1]([O:5][C:6](=[O:28])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[N:37]=[C:31]4[C:30]([F:29])=[CH:35][C:34]([F:36])=[CH:33][N:32]4[C:19]=3[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 27832383,5-Difluoropyridin-2-amineHCID 86691038tert-Butyl (1-{4-[bromo(phenyl)acetyl]phenyl}cyclobutyl)carbamate

Product 1

HCID 66665521{1-[4-(6,8-Difluoro-3-phenyl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl esterYield 10.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

1 g (2.25 mmol) {1-[4-(2-Bromo-2-phenyl-acetyl)-phenyl]-cyclobutyl}-carbamic acid tert.-butyl ester, 292.8 mg (2.25 mmol) 3,5-difluoro-pyridin-2-yl-amine and 900 mg molecular sieves (3A, dried over night at 120° C. in a drying oven) in 20 mL ethanol were heated at reflux in a pressure pipe for 20 hours. The reaction mixture was sucked off via a glass fibre filter and evaporated to dryness. The residue was redissolved in dichloromethane, washed with hydrochloric acid (1 M), saturated sodium bicarbonate and brine and dried (sodium sulfate). After filtration and removal of the solvent the residue was purified by chromatography on silicagel (eluents: hexane/ethyl acetate) yielding 109.9 mg (9.8%) of the pure title compound.

Workup

  1. temperaturewere heated
  2. temperatureat reflux in a pressure pipe for 20 hours
  3. filtrationfilter
  4. customevaporated to dryness
  5. dissolutionThe residue was redissolved in dichloromethane
  6. washwashed with hydrochloric acid (1 M), saturated sodium bicarbonate and brine
  7. dry with materialdried (sodium sulfate)
  8. filtrationAfter filtration and removal of the solvent the residue
  9. customwas purified by chromatography on silicagel (eluents: hexane/ethyl acetate)

Sources & evidence

ORD record
ord-bc31660c522041f4bf7a8df1e6700d0e
Source dataset
uspto-grants-2015_03
Patent number
US08975265B2

Reaction notes

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