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

HRID 1040171Notes

Reaction equation

HRID 1040171 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.CCO.COCCN(S(F)(F)[F:44])CCOC>C(Cl)Cl.O>[F:44][C:24]1([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:18])([F:16])[F:17])[CH:12]=[CH:11][N:10]=4)[CH:7]=[C:2]([CH3:1])[CH:3]=3)=[CH:20][N:21]=2)[CH2:25][CH2:26][S:27][CH2:28][CH2:29]1

Participants

6

Reactant 3

HCID 702EthanolHCID 2734690(Bis(2-methoxyethyl)amino)sulfur trifluorideHCID 672569944-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}-phenyl)-1,3-thiazol-2-yl]tetrahydro-2H-thiopyran-4-ol

Product 1

HCID 58456368N-{3-[2-(4-fluorotetrahydro-2H-thiopyran-4-yl)-1,3-thiazol-5-yl]-5-methylphenyl}-4-(trifluoromethyl)pyrimidin-2-amineYield 74.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of the product of Step 1 (250 mg, 0.552 mmol) in CH2Cl2 (5 ml) were added EtOH (0.05 mL) and Deoxo-fluor (0.509 ml, 2.76 mmol). The reaction was stirred at room temperature for 30 minutes, diluted with water (5 mL) and extracted with EtOAc (2×10 mL). The combined organic layers were washed with brine, dried (MgSO4), filtered and evaporated. Column chromatography on silica (gradient elution, 0 to 25% EtOAc in hexanes) afforded the title compound (0.186 g, 0.409 mmol, 74% yield) as a pale yellow foam. MS ESI: [M+H]+ m/z 455.0. 1H NMR (500 MHz, DMSO-d6) δ 10.29 (s, 1H), 8.83 (d, J=4.9, 1H), 8.10 (d, J=2.7, 1H), 8.03 (bs, 1H), 7.47 (bs, 1H), 7.28 (d, J=4.9, 1H), 7.20 (bs, 1H), 2.94-2.89 (m, 2H), 2.69-2.66 (m, 2H), 2.39-2.75 (m, 7H). rhSYK activity=++.

Workup

  1. extractionextracted with EtOAc (2×10 mL)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. customevaporated

Sources & evidence

ORD record
ord-795d247da17546cd8843db2246e0dfd2
Source dataset
uspto-grants-2013_10
Patent number
US08551984B2

Reaction notes

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