4-Fluorophenol → 1-(2-Cyclopropyl-3-methylimidazo[1,2-a]pyridin-6-yl)-4-((4-fluorophenoxy)methyl)pyridin-2(1H)-one

HRID 2202991Notes

Reaction equation

HRID 2202991 reaction equation
[CH:1]1([C:4]2[N:5]=[C:6]3[CH:11]=[CH:10][C:9]([N:12]4[CH:17]=[CH:16][C:15]([CH2:18][OH:19])=[CH:14][C:13]4=[O:20])=[CH:8][N:7]3[C:21]=2[CH3:22])[CH2:3][CH2:2]1.[F:23][C:24]1[CH:29]=[CH:28][C:27](O)=[CH:26][CH:25]=1.C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>C1COCC1>[CH:1]1([C:4]2[N:5]=[C:6]3[CH:11]=[CH:10][C:9]([N:12]4[CH:17]=[CH:16][C:15]([CH2:18][O:19][C:27]5[CH:28]=[CH:29][C:24]([F:23])=[CH:25][CH:26]=5)=[CH:14][C:13]4=[O:20])=[CH:8][N:7]3[C:21]=2[CH3:22])[CH2:2][CH2:3]1

Participants

6

Reactant 4

HCID 97324-FluorophenolHCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 89690337HCID 89690337, compound

Product 1

HCID 896901851-(2-Cyclopropyl-3-methylimidazo[1,2-a]pyridin-6-yl)-4-((4-fluorophenoxy)methyl)pyridin-2(1H)-oneYield 12.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 1-(2-cyclopropyl-3-methylimidazo[1,2-a]pyridin-6-yl)-4-(hydroxymethyl)pyridin-2(1H)-one (150 mg), 4-fluorophenol (85 mg) and tributylphosphine (307 mg) in THF (20 ml) was added 1,1′-(azodicarbonyl)dipiperidine (386 mg), and the mixture was stirred at 60° C. for 5 h. The reaction mixture was cooled to room temperature, concentrated in vacuo, and diluted with DCM. The mixture was washed with water and brine successively, dried over Na2SO4, concentrated in vacuo and purified by column chromatography (MeOH/DCM) followed by preparative HPLC to afford the title compound (24 mg) as a white solid.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. concentrationconcentrated in vacuo
  3. additiondiluted with DCM
  4. washThe mixture was washed with water and brine successively
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. custompurified by column chromatography (MeOH/DCM)

Sources & evidence

ORD record
ord-5c701066adfc4d5c99c1c178d08b2582
Source dataset
uspto-grants-2016_06
Patent number
US09365540B2

Reaction notes

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