Reaktion #2337615

Reaktionsgleichung

1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-pyrrolo[3,2-b]pyridine-2-carboxylic acid

1-isopropyl-piperidin-4-ylamine hydrochloride

bis(2-oxo-3-oxazolidinyl)phosphinic chloride

→

1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-pyrrolo[3,2-b]pyridine-2-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide

Lösungsmittel

dichloromethane

triethylamine

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONwere added at room temperature
2. 2
   SonstigeAfter removing of the solvent under reduced pressure
3. 3
   Sonstigethe residue was purified by preparative HPLC (
4. 4
   WaschenC18 reverse phase column, elution with a water/acetonitrile gradient with 0.1% trifluoroacetic acid)
5. 5
   workup.ADDITIONThe fractions containing the product
6. 6
   Sonstigewere evaporated
7. 7
   Sonstigeto yield a white residue which
8. 8
   Sonstigewas partitioned between 5 mL aqueous 0.1 N sodium hydroxide solution and 5 mL ethyl acetate
9. 9
   WaschenThe organic layer was washed with additional water
10. 10
    Trocknendried over sodium sulphate
11. 11
    FiltrationAfter filtration and removal of the solvent under reduced pressure
12. 12
    Sonstigea white solid was obtained

Vorschrift

To a suspension of 50 mg 1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-pyrrolo[3,2-b]pyridine-2-carboxylic acid, 36 mg 1-isopropyl-piperidin-4-ylamine hydrochloride and 35 mg bis(2-oxo-3-oxazolidinyl)phosphinic chloride in 1 mL dichloromethane, 77 μl triethylamine were added at room temperature and the mixture was stirred for 16 hours. After removing of the solvent under reduced pressure, the residue was purified by preparative HPLC (C18 reverse phase column, elution with a water/acetonitrile gradient with 0.1% trifluoroacetic acid). The fractions containing the product were evaporated and lyophilized to yield a white residue which was partitioned between 5 mL aqueous 0.1 N sodium hydroxide solution and 5 mL ethyl acetate. The organic layer was washed with additional water and then dried over sodium sulphate. After filtration and removal of the solvent under reduced pressure, a white solid was obtained.

Quelle