Réaction #66175

Équation de réaction

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

Solvants

ethanol

ethanol

Conditions de réaction

Traitement

1. 1
   Températurethe mixture is heated
2. 2
   Températureunder reflux overnight
3. 3
   TempératureAfter cooling
4. 4
   Concentrationthe mixture is concentrated
5. 5
   Autrethe 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
   Concentrationconcentrated
10. 10
    Autrethe 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
    Autreobtained this time
13. 13
    workup.STIRRINGthe mixture is stirred at RT for 2 h
14. 14
    Concentrationconcentrated
15. 15
    Autrethe residue is purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% conc. hydrochloric acid)

Mode opératoire

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.

Source