Hydrochloric Acid → 2-[6-(4-Methylpiperazin-1-yl)-pyrimidin-4-yl]-4-pyridin-3-yl-1,2-dihydro-3H-pyrazol-3-one dihydrochloride

HRID 37897

반응식

HRID 37897 반응식
CN(C)[CH:3]=[C:4]([C:10]1[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=1)[C:5](OCC)=[O:6].[NH:17]([C:19]1[CH:24]=[C:23]([N:25]2[CH2:30][CH2:29][N:28]([CH3:31])[CH2:27][CH2:26]2)[N:22]=[CH:21][N:20]=1)[NH2:18].C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O.C[O-].[Na+].[ClH:50]>C(O)C>[ClH:50].[ClH:50].[CH3:31][N:28]1[CH2:29][CH2:30][N:25]([C:23]2[N:22]=[CH:21][N:20]=[C:19]([N:17]3[C:5](=[O:6])[C:4]([C:10]4[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=4)=[CH:3][NH:18]3)[CH:24]=2)[CH2:26][CH2:27]1

참가 물질

7

반응물 5

HCID 313Hydrochloric AcidHCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 10942334Sodium MethoxideHCID 133936264-Hydrazino-6-(4-methylpiperazin-1-yl)pyrimidineHCID 687048643-(Dimethylamino)-2-pyridin-3-yl-acrylic acid ethyl ester

생성물 1

HCID 250731292-[6-(4-Methylpiperazin-1-yl)-pyrimidin-4-yl]-4-pyridin-3-yl-1,2-dihydro-3H-pyrazol-3-one dihydrochloride

시약·촉매·용매 1

HCID 702Ethanol용매2회

실험 절차

146 mg (663 μmol) of the compound from Example 3A, 115 mg (552 μmol) of the compound from Example 6A and 13 mg (55 μmol) of camphor-10-sulfonic acid are dissolved in 5 ml of anhydrous ethanol, and the mixture is heated under reflux overnight. After cooling, the mixture is concentrated and the residue is purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% conc. hydrochloric acid). The resulting mixture of target product and intermediate is dissolved in 5 ml of anhydrous ethanol, 109 mg (607 μmol) of a 30% strength methanolic sodium methoxide solution are added and the mixture is stirred at RT for 1 h. The mixture is then neutralized with 1 M hydrochloric acid and concentrated, and the residue is purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% conc. hydrochloric acid). The mixture of target product and intermediate obtained this time is again dissolved in 5 ml of anhydrous ethanol, 99 mg (552 μmol) of a 30% strength methanolic sodium methoxide solution are added and the mixture is stirred at RT for 2 h. The mixture is then again neutralized with 1 M hydrochloric acid and concentrated, and the residue is purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% conc. hydrochloric acid). This gives 9 mg (4% of theory) of the title compound.

후처리

  1. temperaturethe mixture is heated
  2. temperatureunder reflux overnight
  3. temperatureAfter cooling
  4. concentrationthe mixture is concentrated
  5. customthe residue is purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% conc. hydrochloric acid)
  6. additionThe resulting mixture of target product and intermediate
  7. dissolutionis dissolved in 5 ml of anhydrous ethanol
  8. addition109 mg (607 μmol) of a 30% strength methanolic sodium methoxide solution are added
  9. concentrationconcentrated
  10. customthe residue is purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% conc. hydrochloric acid)
  11. additionThe mixture of target product and intermediate
  12. customobtained this time
  13. stirringthe mixture is stirred at RT for 2 h
  14. concentrationconcentrated
  15. customthe residue is purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% conc. hydrochloric acid)

출처 및 근거

ORD 기록
ord-c6b2a0dd8d9c46289b0daf00309f0065
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08524699B2

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