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

HRID 2039483ノート

反応式

HRID 2039483 の反応式
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

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒

反応条件

温度
100 °C

実験手順

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 (RP 18 column; mobile phase: acetonitrile/water gradient). Yield: 137 mg (36% of theory)

後処理

  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 (RP 18 column; mobile phase: acetonitrile/water gradient)

出典と根拠

ORDレコード
ord-5ea860552a2441f3baad167981bd47b8
出典データセット
uspto-grants-2013_11
特許番号
US08580778B2

反応ノート

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