Potassium Carbonate → HCID 178513671, compound

HRID 492496Notes

Reaction equation

HRID 492496 reaction equation
[OH:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([NH:8][CH2:9][CH2:10][C:11]2[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=2)[CH2:4][CH2:3]1.Cl[C:19]1[CH:27]=[CH:26][C:22]([C:23]([NH2:25])=[O:24])=[CH:21][N:20]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.C1(C)C=CC=CC=1>[OH:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([NH:8][CH2:9][CH2:10][C:11]2[CH:12]=[CH:13][C:14]([O:17][C:19]3[CH:27]=[CH:26][C:22]([C:23]([NH2:25])=[O:24])=[CH:21][N:20]=3)=[CH:15][CH:16]=2)[CH2:4][CH2:3]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 804566-ChloronicotinamideHCID 178516032HCID 178516032, compound

Product 1

HCID 178513671HCID 178513671, compoundYield 43%

Reagents, catalysts & solvents 1

HCID 21735183Dimethylformamide tolueneSolvent

Procedure

Heat a mixture of the phenol (121.2 mg, 0.52 mmol), 6-chloronicotinamide (121.0 mg, 0.77 mmol), and K2CO3 (213.5 mg, 1.55 mmol) in 3:1 DMF/toluene (6.0 mL) at 165° C. for 3 hours. Quench the reaction with a small amount of H2O and concentrate to dryness, using xylenes to remove DMF azeotropically. Dissolve the residue in MeOH and filter. Concentrate the filtrate and purify by flash chromatography, eluting with 75:15:10 EtOAc/CH2Cl2/2.0 M NH3 in MeOH, to afford the title compound (79.1 mg, 43%): MS ES+ 356.0 (M+H)+, HRMS calcd for C20H26N3O3 356.1974 (M+H)+, found 356.1959, time 0.34 min; HPLC [YMC-Pack Pro C-18 (150×4.6 mm, S-5 microm), acetonitrile in water containing 0.01% concentrated HCl at 1.0 mL/min, 5-95% over 19 min], tR=5.81 min, 100% purity.

Workup

  1. temperatureHeat
  2. customQuench
  3. customthe reaction with a small amount of H2O
  4. concentrationconcentrate to dryness
  5. customto remove DMF azeotropically
  6. dissolutionDissolve the residue in MeOH
  7. filtrationfilter
  8. concentrationConcentrate the filtrate
  9. custompurify by flash chromatography
  10. washeluting with 75:15:10 EtOAc/CH2Cl2/2.0 M NH3 in MeOH

Sources & evidence

ORD record
ord-5bab236d22bd4b418284b44fc4b463ef
Source dataset
uspto-grants-2009_05
Patent number
US07531557B2

Reaction notes

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