4-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}-phenyl)-1,3-thiazol-2-yl]tetrahydro-2H-thiopyran-4-ol → HCID 58456228, compound

HRID 410673Notes

Reaction equation

HRID 410673 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([C:19]2[S:23][C:22]([C:24]3(O)[CH2:29][CH2:28][S:27][CH2:26][CH2:25]3)=[N:21][CH:20]=2)[CH:5]=[C:6]([NH:8][C:9]2[N:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[CH:11][N:10]=2)[CH:7]=1.CS(O)(=O)=O.O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O>C([O-])(O)=O.[Na+]>[S:27]1[CH2:26][CH:25]=[C:24]([C:22]2[S:23][C:19]([C:4]3[CH:5]=[C:6]([NH:8][C:9]4[N:14]=[C:13]([C:15]([F:16])([F:17])[F:18])[CH:12]=[CH:11][N:10]=4)[CH:7]=[C:2]([CH3:1])[CH:3]=3)=[CH:20][N:21]=2)[CH2:29][CH2:28]1

Participants

4

Reactant 2

HCID 672569944-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}-phenyl)-1,3-thiazol-2-yl]tetrahydro-2H-thiopyran-4-olHCID 86584057Phosphorus Pentoxide-Methanesulfonic Acid

Product 1

HCID 58456228HCID 58456228, compoundYield 41.7%

Reagents, catalysts & solvents 1

HCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
70 °C

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=+++.

Workup

  1. temperatureThe dark brown reaction mixture was cooled to room temperature
  2. extractionextracted with EtOAc (2×5 mL)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customevaporated

Sources & evidence

ORD record
ord-39c8f7b087074f5d99f141741a620c5e
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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