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 562461노트

반응식

HRID 562461 반응식
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

참가 물질

5

반응물 3

HCID 6422Trifluoroacetic acidHCID 462211044-(4-Cyclobutylpiperazin-1-yl)-6-hydrazinopyrimidineHCID 66726233Ethyl 3-(dimethylamino)-2-(1H-1,2,3-triazol-1-yl)acrylate

생성물 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

시약·촉매·용매 1

HCID 8857Ethyl Acetate용매

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온도
100 °C

실험 절차

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)

후처리

  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)

출처 및 근거

ORD 기록
ord-37e9f2fc515c4cb0a0460671c7a455c2
출처 데이터셋
uspto-grants-2011_11
특허 번호
US08067407B2

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