Reaction #497855

Reaction equation

4-[5-(3-Methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]tetrahydro-2H-thiopyran-4-ol

4-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}-phenyl)-1,3-thiazol-2-yl]tetrahydro-2H-thiopyran-4-ol

Eaton's reagent

→

title compound

Yield 41.7%

N-{3-[2-(3,6-dihydro-2H-thiopyran-4-yl)-1,3-thiazol-5-yl]-5-methylphenyl}-4-(trifluoromethyl)pyrimidin-2-amine

Yield 41.7%

Solvents

NaHCO3

Conditions

Workup

1. 1
   TemperatureThe dark brown reaction mixture was cooled to room temperature
2. 2
   Extractionextracted with EtOAc (2×5 mL)
3. 3
   WashThe combined organic layers were washed with brine
4. 4
   Dryingdried (MgSO4)
5. 5
   Filtrationfiltered
6. 6
   Otherevaporated

Procedure

4-[5-(3-Methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]tetrahydro-2H-thiopyran-4-ol (Step 1, Example 132, 250 mg, 0.552 mmol) was combined with Eaton's reagent (1.0 mL, 6.3 mmol) and stirred at 70° C. for 3 hrs. The dark brown reaction mixture was cooled to room temperature, carefully neutralized/diluted with aqueous saturated NaHCO3 (4 mL) and extracted with EtOAc (2×5 mL). The combined organic layers were washed with brine, dried (MgSO4), filtered and evaporated. Column chromatography on silica (gradient elution, 0 to 40% EtOAc in hexanes) afforded the title compound (0.100 g, 0.23 mmol, 41.7% yield) as a yellow foam. MS ESI: [M+H]+ m/z 435.0. 1H NMR (500 MHz, DMSO-d6) δ 10.27 (s, 1H), 8.83 (d, J=4.9, 1H), 8.06 (s, 1H), 8.01 (bs, 1H), 7.45 (bs, 1H), 7.28 (d, J=4.9, 1H), 7.18 (bs, 1H), 6.81 (m, 1H), 3.39-3.35 (m, 2H), 2.85-2.83 (m, 2H), 2.77-2.75 (m, 2H), 2.31 (s, 3H). rhSYK activity=+++.

Source