Sodium Carbonate → 5-(4-methoxyphenyl)-2-(1H-pyrazol-5-yl)oxazole-4-carboxamide

HRID 389741Notes

Reaction equation

HRID 389741 reaction equation
I[C:2]1[O:3][C:4]([C:10]2[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=2)=[C:5]([C:7]([NH2:9])=[O:8])[N:6]=1.[NH:18]1[C:22](B(O)O)=[CH:21][CH:20]=[N:19]1.C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C.CS(C)=O.CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:17][O:16][C:13]1[CH:14]=[CH:15][C:10]([C:4]2[O:3][C:2]([C:20]3[NH:19][N:18]=[CH:22][CH:21]=3)=[N:6][C:5]=2[C:7]([NH2:9])=[O:8])=[CH:11][CH:12]=1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 112519791H-Pyrazole-5-boronic acidHCID 685209522-Iodo-5-(4-methoxyphenyl)oxazole-4-carboxamide

Product 1

HCID 595876645-(4-methoxyphenyl)-2-(1H-pyrazol-5-yl)oxazole-4-carboxamideYield 42.9%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst2×HCID 679Dimethyl SulfoxideSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
150 °C

Procedure

To a mixture of 2-iodo-5-(4-methoxyphenyl)oxazole-4-carboxamide (0.025 g, 0.07 mmol), 1H-pyrazole-5-boronic acid (0.020 g, 0.18 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.003 g, 0.004 mmol) in acetonitrile (2 mL) and DMSO (0.5 mL) was added a 1M sodium carbonate solution (0.1 mL, 0.1 mmol) and the reaction heated in the microwave at 150° C. for 15 minutes. A further portion of [1,1′-bis(diphenylphosphino)ferrocene]dichloro-palladium(II) (0.003 g, 0.004 mmol) was added and the mixture heated at 150° C. for a further 10 minutes in the microwave. The reaction was diluted with EtOAc and washed 1M sodium carbonate solution. The aqueous phase was extracted with EtOAc and the combined organic phases were washed with brine, dried over MgSO4 and passed through a MP-SH resin cartridge (500 mg). The solvent was removed in vacuo and the residue purified by preparative HPLC to afford 5-(4-methoxyphenyl)-2-(1H-pyrazol-5-yl)oxazole-4-carboxamide (0.008 g, 0.03 mmol, 38%) as a white solid. 1H NMR (DMSO) 3.84 (3H, s), 6.90 (1H, br. d), 7.09 (2H, d), 7.62 (1H, br. s), 7.67 (1H, br. s), 7.97 (1H, br. s), 8.27 (2H, br. d), 13.50 (1H, br. s). LCMS (2) Rt: 1.98 min; m/z (ES+) 285.

Workup

  1. temperaturethe mixture heated at 150° C. for a further 10 minutes in the microwave
  2. washwashed 1M sodium carbonate solution
  3. extractionThe aqueous phase was extracted with EtOAc
  4. washthe combined organic phases were washed with brine
  5. dry with materialdried over MgSO4
  6. customThe solvent was removed in vacuo
  7. customthe residue purified by preparative HPLC

Sources & evidence

ORD record
ord-959134766f364dbbb4b04994d8fa8425
Source dataset
uspto-grants-2013_02
Patent number
US08378095B2

Reaction notes

Loading…