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

HRID 2039484ノート

反応式

HRID 2039484 の反応式
FC(F)(F)C(O)=O.CN(C)[CH:10]=[C:11]([N:17]1[CH:21]=[CH:20][N:19]=[N:18]1)[C:12](OCC)=[O:13].[CH:23]1([N:27]2[CH2:32][CH2:31][N:30]([C:33]3[CH:38]=[C:37]([NH:39][NH2:40])[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[CH2:28][CH2:29][N:30]([C:33]3[N:34]=[CH:35][N:36]=[C:37]([N:39]4[C:12](=[O:13])[C:11]([N:17]5[CH:21]=[CH:20][N:19]=[N:18]5)=[CH:10][NH:40]4)[CH:38]=3)[CH2:31][CH2:32]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 66726233Ethyl 3-(dimethylamino)-2-(1H-1,2,3-triazol-1-yl)acrylate

生成物 1

HCID 444643702-[6-(4-Cyclobutylpiperazin-1-yl)pyrimidin-4-yl]-4-(1H-1,2,3-triazol-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 8A 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: 195 mg (51% 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 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)

出典と根拠

ORDレコード
ord-98043043d345421babc1cb85dff13829
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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