Reaktion #66187

Reaktionsgleichung

ethanol

compound

2-(6-Chloropyrimidin-4-yl)-4-pyridin-3-yl-1,2-dihydro-3H-pyrazol-3-one

N,N-diisopropylethylamine

azetidin-3-ol hydrochloride

→

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

Lösungsmittel

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigereacted at 120° C. in a single-mode microwave oven (CEM Explorer) for 20 min
2. 2
   Sonstigethe mixture is again reacted in a single-mode microwave oven (CEM Explorer) for 20 min
3. 3
   SonstigeThe mixture is then reacted initially at 120° C. for a further 60 min
4. 4
   SonstigeThe mixture is then separated directly by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% TFA)
5. 5
   Einengenconcentrated on a rotary evaporator
6. 6
   Sonstigethe residue is dried under high vacuum
7. 7
   FiltrationThe solid is filtered off
8. 8
   Waschenwashed with tert-butyl methyl ether
9. 9
   Sonstigedried under high vacuum

Vorschrift

100 mg (0.4 mmol) of the compound from Example 23, 94 mg (0.7 mmol) of N,N-diisopropylethylamine and 80 mg (0.7 mmol) of azetidin-3-ol hydrochloride are suspended in 3 ml of THF and reacted at 120° C. in a single-mode microwave oven (CEM Explorer) for 20 min. 2 ml of ethanol are then added, and the mixture is again reacted in a single-mode microwave oven (CEM Explorer) for 20 min. The mixture is then reacted initially at 120° C. for a further 60 min and then at 175° C. for 60 min in a single-mode microwave oven (CEM Explorer). The mixture is then separated directly by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% TFA). The product-containing fractions are combined and concentrated on a rotary evaporator, and the residue is dried under high vacuum. The residue is then stirred in 5 ml of a 4 N solution of hydrogen chloride in dioxane for 30 min. The solid is filtered off, washed with tert-butyl methyl ether and dried under high vacuum.

Quelle