Sodium Carbonate → 6-(3,5-Difluorophenyl)-7-methyl-5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one

HRID 1896324Notes

Reaction equation

HRID 1896324 reaction equation
I[C:2]1[C:7](=[O:8])[N:6]2[CH:9]=[CH:10][S:11][C:5]2=[N:4][C:3]=1[CH3:12].C([O-])([O-])=O.[Na+].[Na+].[F:19][C:20]1[CH:21]=[C:22](B(O)O)[CH:23]=[C:24]([F:26])[CH:25]=1>C1(C)C=CC=CC=1.O.C(O)C>[F:19][C:20]1[CH:21]=[C:22]([C:2]2[C:7](=[O:8])[N:6]3[CH:9]=[CH:10][S:11][C:5]3=[N:4][C:3]=2[CH3:12])[CH:23]=[C:24]([F:26])[CH:25]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 2734338(3,5-Difluorophenyl)boronic acidHCID 667535716-Iodo-7-methyl-5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one

Product 1

HCID 667534716-(3,5-Difluorophenyl)-7-methyl-5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

To a solution of Step 2 intermediate (0.300 g, 1.027 mmol) in toluene (10 ml) was added Pd[(C6H5)3P]4 [tetrakis(triphenylphosphine)palladium(0)] (0.048 g. 0.042 mmol) and a solution of Na2CO3 (0.653 g, 6.162 mmol) in water (4 ml). A solution of 3,5-difluorophenylboronic acid (6.5 g, 44.235 mmol) in ethanol (6 ml) was added to the reaction mixture and it was refluxed for 1.5 h. After completion of the reaction mixture, the solvent was concentrated in vacuo, the residue partitioned between ethyl acetate (200 ml) and water (50 ml). The organic layer was washed with brine (50 ml) and dried over anhydrous Na2SO4 to afford a crude product which was purified by silica gel column chromatography using 10% ethyl acetate in chloroform to give 280 mg of the product as an off-white solid; 1H NMR (300 MHz, DMSO-d6) δ 2.19 (s, 3H), 7.53 (d, J=7.8 Hz, 3H), 7.88 (d, J=7.8 Hz, 1H) 8.02 (d, J=4.8 Hz, 1H); ESI-MS (m/z) 276.31 (M−H)−.

Workup

  1. temperaturewas refluxed for 1.5 h
  2. concentrationAfter completion of the reaction mixture, the solvent was concentrated in vacuo
  3. customthe residue partitioned between ethyl acetate (200 ml) and water (50 ml)
  4. washThe organic layer was washed with brine (50 ml)
  5. dry with materialdried over anhydrous Na2SO4
  6. customto afford a crude product which
  7. customwas purified by silica gel column chromatography

Sources & evidence

ORD record
ord-ef3567019a8a4f569f7fe7b10e596781
Source dataset
uspto-grants-2013_08
Patent number
US08518955B2

Reaction notes

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