반응 #66175

반응 방정식

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

용매

ethanol

ethanol

반응 조건

후처리

1. 1
   온도the mixture is heated
2. 2
   온도under reflux overnight
3. 3
   온도After cooling
4. 4
   농축the mixture is concentrated
5. 5
   기타the 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
   농축concentrated
10. 10
    기타the 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
    기타obtained this time
13. 13
    workup.STIRRINGthe mixture is stirred at RT for 2 h
14. 14
    농축concentrated
15. 15
    기타the residue is purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% conc. hydrochloric acid)

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.

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