Trifluoroacetic acid → HCID 58456214, compound

HRID 1040001Notes

Reaction equation

HRID 1040001 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([C:19]2[S:23][C:22]([C:24](O)([CH3:26])[CH3:25])=[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.[SiH](CC)(CC)CC.C(O)(C(F)(F)F)=O>C(Cl)Cl.C(OCC)(=O)C>[CH3:1][C:2]1[CH:7]=[C:6]([NH:8][C:9]2[N:14]=[C:13]([C:15]([F:16])([F:18])[F:17])[CH:12]=[CH:11][N:10]=2)[CH:5]=[C:4]([C:19]2[S:23][C:22]([CH:24]([CH3:26])[CH3:25])=[N:21][CH:20]=2)[CH:3]=1

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acid2×HCID 12052Triethylsilane2×HCID 58456157HCID 58456157, compound

Product 1

HCID 58456214HCID 58456214, compoundYield 57.3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

To a stirred solution of 2-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl}amino]phenyl)-1,3-thiazol-2-yl]propan-2-ol (Example 4, 58 mg, 0.15 mmol) in DCM (1.5 mL) were added Et3SiH (0.18 mL, 1.1 mmol) and TFA (0.17 mL, 2.2 mmol). The reaction mixture was heated to 60° C. for 3 hr. Additional Et3SiH (0.18 mL) and TFA (0.11 mL) were added and the reaction was then heated to 80° C. for 1 d. The mixture was cooled to room temperature, diluted with ethyl acetate (75 mL) and washed with saturated aqueous NRHCO3 solution, water, and brine. The solution was dried over anhydrous sodium sulfate, concentrated, and purified by flash chromatography to give N-{3-methyl-5-[2-(1-methylethyl)-1,3-thiazol-5-yl]phenyl}-4-(trifluoromethyl)pyrimidin-2-amine (31.7 mg, 0.084 mmol, 57.3% yield) as a white solid. APCI: [M+H]+ m/z 379.1. 1H NMR (500 MHz, DMSO-d6) δ 10.25 (s, 1H), 8.83 (d, J=4.9, 1H), 7.98 (s, 1H), 7.93 (s, 1H), 7.44 (s, 1H), 7.28 (d, J=4.9, 1H), 7.14 (s, 1H), 3.27 (dt, J=6.9, 13.7, 1H), 2.31 (s, 3H), 1.34 (d, J=6.9, 6H). rhSYK activity=+++

Workup

  1. temperaturethe reaction was then heated to 80° C. for 1 d
  2. temperatureThe mixture was cooled to room temperature
  3. washwashed with saturated aqueous NRHCO3 solution, water, and brine
  4. dry with materialThe solution was dried over anhydrous sodium sulfate
  5. concentrationconcentrated
  6. custompurified by flash chromatography

Sources & evidence

ORD record
ord-18bda48e998d4998adaccc8683342153
Source dataset
uspto-grants-2013_10
Patent number
US08551984B2

Reaction notes

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