Reaktion #66175

Reaktionsgleichung

sodium methoxide

compound

Ethyl 3-(dimethylamino)-2-pyridin-3-ylacrylate

compound

4-Hydrazino-6-(4-methylpiperazin-1-yl)pyrimidine

camphor-10-sulfonic acid

hydrochloric acid

→

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

Lösungsmittel

ethanol

ethanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturthe mixture is heated
2. 2
   Temperaturunder reflux overnight
3. 3
   TemperaturAfter cooling
4. 4
   Einengenthe mixture is concentrated
5. 5
   Sonstigethe residue is purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% conc. hydrochloric acid)
6. 6
   workup.ADDITIONThe resulting mixture of target product and intermediate
7. 7
   workup.DISSOLUTIONis dissolved in 5 ml of anhydrous ethanol
8. 8
   workup.ADDITION109 mg (607 μmol) of a 30% strength methanolic sodium methoxide solution are added
9. 9
   Einengenconcentrated
10. 10
    Sonstigethe residue is purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% conc. hydrochloric acid)
11. 11
    workup.ADDITIONThe mixture of target product and intermediate
12. 12
    Sonstigeobtained this time
13. 13
    workup.STIRRINGthe mixture is stirred at RT for 2 h
14. 14
    Einengenconcentrated
15. 15
    Sonstigethe residue is purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% conc. hydrochloric acid)

Vorschrift

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.

Quelle