Sodium Carbonate → N-[4-(5-formyl-4-phenyl-1,3-thiazol-2-yl)pyridin-2-yl]acetamide

HRID 1530133Notes

Reaction equation

HRID 1530133 reaction equation
F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C.C(=O)([O-])[O-].[Na+].[Na+].[C:25]1(B(O)O)[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.Cl[C:35]1[N:36]=[C:37]([C:42]2[CH:47]=[CH:46][N:45]=[C:44]([NH:48][C:49](=[O:51])[CH3:50])[CH:43]=2)[S:38][C:39]=1[CH:40]=[O:41]>COCCOC.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:40]([C:39]1[S:38][C:37]([C:42]2[CH:47]=[CH:46][N:45]=[C:44]([NH:48][C:49](=[O:51])[CH3:50])[CH:43]=2)=[N:36][C:35]=1[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[O:41]

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 2734635Tri-tert-butylphosphine tetrafluoroborateHCID 86649613N-[4-(4-chloro-5-formyl-1,3-thiazol-2-yl)pyridin-2-yl]acetamide

Product 1

HCID 86649614N-[4-(5-formyl-4-phenyl-1,3-thiazol-2-yl)pyridin-2-yl]acetamideYield 43.1%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

Tris(dibenzylideneacetone)dipalladium(0) (0.0162 g, 0.0177 mmol) and tri-t-butylphosphonium tetrafluoroborate (0.0103 g, 0.0355 mmol) were weighed into a round bottom flask and dissolved in DME (3 mL). The mixture was sonicated for 15 min under atmosphere of Argon. After addition of water (1 mL), sodium carbonate (0.226 g, 2.13 mmol) was added to the dark purple solution followed by phenylboronic acid (0.173 g, 1.42 mmol) and N-[4-(4-chloro-5-formyl-1,3-thiazol-2-yl)pyridin-2-yl]acetamide (0.200 g, 0.710 mmol). The resulting mixture was stirred for 10 h at 80° C., cooled to room temperature, diluted with water and extracted with DCM (3×5 mL). The organics were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated. The result mixture was purified by ISCO column with 0-5% MeOH in DCM in 10 min. Fractions containing product were combined and solvent was removed under reduced pressure to give crude material (0.099 g, 43%), which was used in the next step without further purification. LCMS: (FA) ES+ 324.

Workup

  1. customThe mixture was sonicated for 15 min under atmosphere of Argon
  2. additionwas added to the dark purple solution
  3. temperaturecooled to room temperature
  4. extractionextracted with DCM (3×5 mL)
  5. washThe organics were washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe result mixture was purified by ISCO column with 0-5% MeOH in DCM in 10 min
  10. additionFractions containing product
  11. customsolvent was removed under reduced pressure

Sources & evidence

ORD record
ord-5971a74d3bd84e3bbc554392faaac069
Source dataset
uspto-grants-2015_07
Patent number
US09090601B2

Reaction notes

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