Cesium carbonate → Tert-butyl 2-(2-phenylpyrimidin-5-yl)thiazole-4-carboxylate

HRID 42313Notes

Reaction equation

HRID 42313 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].[C:7]([O:11][C:12]([C:14]1[N:15]=[CH:16][S:17][CH:18]=1)=[O:13])([CH3:10])([CH3:9])[CH3:8].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.Br[C:62]1[CH:63]=[N:64][C:65]([C:68]2[CH:73]=[CH:72][CH:71]=[CH:70][CH:69]=2)=[N:66][CH:67]=1>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:68]1([C:65]2[N:64]=[CH:63][C:62]([C:16]3[S:17][CH:18]=[C:14]([C:12]([O:11][C:7]([CH3:10])([CH3:8])[CH3:9])=[O:13])[N:15]=3)=[CH:67][N:66]=2)[CH:69]=[CH:70][CH:71]=[CH:72][CH:73]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 143877455-Bromo-2-phenylpyrimidineHCID 16744294Tert-butyl 1,3-thiazole-4-carboxylate

Product 1

HCID 59252449Tert-butyl 2-(2-phenylpyrimidin-5-yl)thiazole-4-carboxylate

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

In a sealed tube, cesium carbonate (1.95 g, 6.00 mmol), tert-butyl-4-thiazolecarboxylate (556 mg, 3.00 mmol; prepared according to the procedure described in Organic Letters, 2008, 10(13), 2909), palladium(II) acetate (47 mg, 0.21 mmol) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (240 mg, 0.42 mmol) were combined with 5-bromo-2-phenylpyrimidine (705 mg, 3.00 mmol) in dry DMF (11 mL) and the mixture heated at 110° C. for 18 hours with stirring. The mixture was cooled to room temperature and filtered through Celite washing with hot ethyl acetate. Solvent was removed under reduced pressure and the residue purified by silica gel flash chromatography (9:1 to 3:2 v/v hexane-ethyl acetate gradient) through a 40-g Silicycle® flash silica cartridge. The title compound was obtained as a white solid (646 mg, 63% yield); Rf 0.75 with 1:1 v/v hexane-ethyl acetate; 1H-NMR (300 MHz; CDCl3) δ 9.37 (s, 2H), 8.52 (dd, 2H), 8.15 (s, 1H), 7.54 (m, 3H), 1.64 (s, 9H); MS (ESI+) m/z 340 (M+1); H-PGDS FPBA IC50: 5.9 μM.

Workup

  1. customprepared
  2. temperatureThe mixture was cooled to room temperature
  3. filtrationfiltered through Celite
  4. washwashing with hot ethyl acetate
  5. customSolvent was removed under reduced pressure
  6. customthe residue purified by silica gel flash chromatography (9:1 to 3:2 v/v hexane-ethyl acetate gradient) through a 40-g Silicycle® flash silica cartridge

Sources & evidence

ORD record
ord-ce138f09324d4eb0902d9d02ff391894
Source dataset
uspto-grants-2013_09
Patent number
US08536185B2

Reaction notes

Loading…