Potassium Carbonate → Methyl 2-((4-(4-(3-cyclobutylureido)-3-fluorobenzoyl)piperazin-1-yl)methyl)isonicotinate

HRID 408880Notes

Reaction equation

HRID 408880 reaction equation
CS([CH2:5][C:6]1[CH:7]=[C:8]([CH:13]=[CH:14][N:15]=1)[C:9]([O:11][CH3:12])=[O:10])(=O)=O.[CH:16]1([NH:20][C:21]([NH:23][C:24]2[CH:29]=[CH:28][C:27]([C:30]([N:32]3[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]3)=[O:31])=[CH:26][C:25]=2[F:38])=[O:22])[CH2:19][CH2:18][CH2:17]1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[CH:16]1([NH:20][C:21](=[O:22])[NH:23][C:24]2[CH:29]=[CH:28][C:27]([C:30]([N:32]3[CH2:37][CH2:36][N:35]([CH2:5][C:6]4[CH:7]=[C:8]([CH:13]=[CH:14][N:15]=4)[C:9]([O:11][CH3:12])=[O:10])[CH2:34][CH2:33]3)=[O:31])=[CH:26][C:25]=2[F:38])[CH2:17][CH2:18][CH2:19]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 666611341-Cyclobutyl-3-(2-fluoro-4-(piperazine-1-carbonyl)phenyl)ureaHCID 66661272Methyl 2-(methylsulfonylmethyl)isonicotinate

Product 1

HCID 66661722Methyl 2-((4-(4-(3-cyclobutylureido)-3-fluorobenzoyl)piperazin-1-yl)methyl)isonicotinateYield 58.6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Methyl 2-(methylsulfonylmethyl)isonicotinate (2.99 mmol, 0.686 g), 1-cyclobutyl-3-(2-fluoro-4-(piperazine-1-carbonyl)phenyl)urea (2.99 mmol, 0.959 g) and potassium carbonate (8.98 mmol, 1.241 g) were combined and heated to 40° C. in acetonitrile (20 mL) for 2 hours. The reaction mixture was concentrated at reduced pressure and the residue taken up in dichloromethane. The organic phase was dried over sodium sulfate and concentrated under vacuum. The residue was purified by silica chromatography (eluting with a solvent gradient from dichloromethane to 6% methanol/dichloromethane) to afford the title compound (822 mg). MS (ESI) m/z 470.5 [M+H]+

Workup

  1. concentrationThe reaction mixture was concentrated at reduced pressure
  2. dry with materialThe organic phase was dried over sodium sulfate
  3. concentrationconcentrated under vacuum
  4. customThe residue was purified by silica chromatography (
  5. washeluting with a solvent gradient from dichloromethane to 6% methanol/dichloromethane)

Sources & evidence

ORD record
ord-6f380e94ded24c6a87398a29c959534b
Source dataset
uspto-grants-2014_06
Patent number
US08759352B2

Reaction notes

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