Trifluoroacetic acid → 1-{2-[6-(4-Cyclobutylpiperazin-1-yl)pyrimidin-4-yl]-3-oxo-2,3-dihydro-1H-pyrazol-4-yl}-1H-imidazole-4-carbonitrile

HRID 2039485Notes

Reaction equation

HRID 2039485 reaction equation
FC(F)(F)C(O)=O.C[N:9]([CH:11]=[C:12]([N:18]1[CH:22]=[C:21]([C:23]#[N:24])[N:20]=[CH:19]1)[C:13]([O:15]CC)=O)C.[CH:25]1([N:29]2[CH2:34][CH2:33][N:32]([C:35]3[CH:40]=[C:39]([NH:41]N)[N:38]=[CH:37][N:36]=3)[CH2:31][CH2:30]2)[CH2:28][CH2:27][CH2:26]1>C(OCC)(=O)C>[CH:25]1([N:29]2[CH2:34][CH2:33][N:32]([C:35]3[N:36]=[CH:37][N:38]=[C:39]([N:41]4[C:13](=[O:15])[C:12]([N:18]5[CH:22]=[C:21]([C:23]#[N:24])[N:20]=[CH:19]5)=[CH:11][NH:9]4)[CH:40]=3)[CH2:31][CH2:30]2)[CH2:26][CH2:27][CH2:28]1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 462211044-(4-Cyclobutylpiperazin-1-yl)-6-hydrazinopyrimidineHCID 66726020Ethyl 3-(N,N-dimethylamino)-2-(4-cyano-1H-imidazol-1-yl)acrylate

Product 1

HCID 444646071-{2-[6-(4-Cyclobutylpiperazin-1-yl)pyrimidin-4-yl]-3-oxo-2,3-dihydro-1H-pyrazol-4-yl}-1H-imidazole-4-carbonitrile

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

16 μl (23 mg, 0.2 mmol) of trifluoroacetic acid are added to a mixture of 236 mg (1.0 mmol) of the compound from Example 6A and 250 mg (1.0 mmol) of the compound from Example 9A in 4 ml of ethyl acetate, and the mixture is stirred at 100° C. for 20 h. The reaction mixture is concentrated under reduced pressure, more ethyl acetate and trifluoroacetic acid (the same amounts as above) are added and the mixture is stirred at 100° C. for 3 d. The reaction mixture is cooled to RT, and the precipitated solid is filtered off and washed with diethyl ether. The residue is suspended in 2 ml of water, dissolved by adding aqueous 1 N sodium hydroxide solution (pH=9-10) and purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient). Yield: 219 mg (56% of theory)

Workup

  1. concentrationThe reaction mixture is concentrated under reduced pressure, more ethyl acetate and trifluoroacetic acid (the same amounts as above)
  2. additionare added
  3. stirringthe mixture is stirred at 100° C. for 3 d
  4. temperatureThe reaction mixture is cooled to RT
  5. filtrationthe precipitated solid is filtered off
  6. washwashed with diethyl ether
  7. dissolutiondissolved
  8. additionby adding aqueous 1 N sodium hydroxide solution (pH=9-10)
  9. custompurified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient)

Sources & evidence

ORD record
ord-654d555929404f159eb30b8fdc5bed6d
Source dataset
uspto-grants-2013_11
Patent number
US08580778B2

Reaction notes

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