Trifluoroacetic acid → 5-[3-[[4-(Trifluoromethyl)pyrimidin-2-yl]amino]phenyl]-1,3-thiazol-2-amine

HRID 1028093Notes

Reaction equation

HRID 1028093 reaction equation
C(OC(=O)[NH:7][C:8]1[S:9][C:10]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([NH:19][C:20]3[N:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[CH:22][N:21]=3)[CH:14]=2)=[CH:11][N:12]=1)(C)(C)C.FC(F)(F)C(O)=O>C(Cl)Cl>[NH2:7][C:8]1[S:9][C:10]([C:13]2[CH:14]=[C:15]([NH:19][C:20]3[N:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[CH:22][N:21]=3)[CH:16]=[CH:17][CH:18]=2)=[CH:11][N:12]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86674323Tert-butyl[5-(3-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]carbamate

Product 1

HCID 532515515-[3-[[4-(Trifluoromethyl)pyrimidin-2-yl]amino]phenyl]-1,3-thiazol-2-amineYield 69.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of tert-butyl[5-(3-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]carbamate (56 mg, 0.128 mmol) in CH2Cl2 (2 mL) at room temperature, under nitrogen, was added trifluoroacetic acid (0.197 mL, 2.56 mmol). The mixture was stirred at room temperature for 17 hours and concentrated to dryness. The residue was partitioned between ethyl acetate and 5% NaHCO3. The aqueous layer was extracted twice with ethyl acetate and the combined organic fractions were washed with water and brine, dried over Na2SO4 and concentrated. The product was purified by column chromatography on silica gel (ethyl acetate/dichloromethane) to afford N-[3-(2-amino-1,3-thiazol-5-yl)phenyl]-4-(trifluoromethyl)-pyrimidin-2-amine (30.1 mg, 69.7%) as a beige solid. APCI [M+H]+ m/z 338.1 1H NMR (400 MHz, Acetone-d6): δ 9.21 (br s, 1H); 8.82 (d, J=4.9 Hz, 1H); 8.12 (s, 1H); 7.67 (d, J=8.2 Hz, 1H); 7.37 (s, 1H); 7.33 (t, J=8.0 Hz, 1H); 7.24 (d, J=4.9 Hz, 1H); 7.18 (d, J=7.8 Hz, 1H); 6.48-6.41 (m, 2H). rhSYK activity=+++

Workup

  1. concentrationconcentrated to dryness
  2. customThe residue was partitioned between ethyl acetate and 5% NaHCO3
  3. extractionThe aqueous layer was extracted twice with ethyl acetate
  4. washthe combined organic fractions were washed with water and brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customThe product was purified by column chromatography on silica gel (ethyl acetate/dichloromethane)

Sources & evidence

ORD record
ord-1732051e72b444bab1b812b22d1cd658
Source dataset
uspto-grants-2014_05
Patent number
US08735417B2

Reaction notes

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