Trifluoroacetic acid → 2-[6-(4-Cyclobutylpiperazin-1-yl)pyrimidin-4-yl]-4-(1H-imidazol-1-yl)-1,2-dihydro-3H-pyrazol-3-one

HRID 562460Notes

Reaction equation

HRID 562460 reaction equation
FC(F)(F)C(O)=O.C[N:9]([CH:11]=[C:12]([N:18]1[CH:22]=[CH:21][N:20]=[CH:19]1)[C:13]([O:15]CC)=O)C.[CH:23]1([N:27]2[CH2:32][CH2:31][N:30]([C:33]3[CH:38]=[C:37]([NH:39]N)[N:36]=[CH:35][N:34]=3)[CH2:29][CH2:28]2)[CH2:26][CH2:25][CH2:24]1>C(OCC)(=O)C>[CH:23]1([N:27]2[CH2:32][CH2:31][N:30]([C:33]3[N:34]=[CH:35][N:36]=[C:37]([N:39]4[C:13](=[O:15])[C:12]([N:18]5[CH:22]=[CH:21][N:20]=[CH:19]5)=[CH:11][NH:9]4)[CH:38]=3)[CH2:29][CH2:28]2)[CH2:24][CH2:25][CH2:26]1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 462211044-(4-Cyclobutylpiperazin-1-yl)-6-hydrazinopyrimidineHCID 66726242Ethyl 3-(N,N-dimethylamino)-2-(1H-imidazol-1-yl)acrylate

Product 1

HCID 444643692-[6-(4-Cyclobutylpiperazin-1-yl)pyrimidin-4-yl]-4-(1H-imidazol-1-yl)-1,2-dihydro-3H-pyrazol-3-one

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 211 mg (1.0 mmol) of the compound from Example 5A 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 20 h. The reaction mixture is cooled to RT, and the precipitated solid is filtered off and washed with diethyl ether. The residue is pre-purified by column chromatography on silica gel (mobile phase dichloromethane/methanol/ammonia 10/2/0.2) and purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient). Yield: 137 mg (36% 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 20 h
  4. temperatureThe reaction mixture is cooled to RT
  5. filtrationthe precipitated solid is filtered off
  6. washwashed with diethyl ether
  7. customThe residue is pre-purified by column chromatography on silica gel (mobile phase dichloromethane/methanol/ammonia 10/2/0.2)
  8. custompurified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient)

Sources & evidence

ORD record
ord-1db3aeac1de547188192103e277c4eff
Source dataset
uspto-grants-2011_11
Patent number
US08067407B2

Reaction notes

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