Reaktion #588560

Reaktionsgleichung

hydrochloric acid

t-butyl 4-[7-(2-butynyl)-2-chloro-1-methyl-6-oxo-6,7-dihydro-1H-purin-8-yl]piperazine-1-carboxylate

ethyl 1-hydroxycyclopropanecarboxylate

sodium hydride

→

t-butyl 4-[7-(2-butynyl)-2-(1-ethoxycarbonylcyclopropyloxy)-1-methyl-6-oxo-6,7-dihydro-1H-purin-8-yl]piperazine-1-carboxylate

Lösungsmittel

N-methylpyrrolidone

Reaktionsbedingungen

Aufarbeitung

1. 1
   Extraktionthe mixture was extracted with ethyl acetate
2. 2
   EinengenThe organic layer was concentrated

Vorschrift

20 mg of t-butyl 4-[7-(2-butynyl)-2-chloro-1-methyl-6-oxo-6,7-dihydro-1H-purin-8-yl]piperazine-1-carboxylate and 20 mg of ethyl 1-hydroxycyclopropanecarboxylate were dissolved in 0.2 ml of N-methylpyrrolidone, and 10 mg of sodium hydride was added thereto. The mixture was stirred at room temperature overnight. 1N hydrochloric acid was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was concentrated to give 63 mg of t-butyl 4-[7-(2-butynyl)-2-(1-ethoxycarbonylcyclopropyloxy)-1-methyl-6-oxo-6,7-dihydro-1H-purin-8-yl]piperazine-1-carboxylate. This compound was dissolved in a solution consisting of 0.4 ml of ethanol and 0.1 ml of a 5N aqueous sodium hydroxide solution, and the mixture was stirred at 50° C. overnight. 1N hydrochloric acid solution was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was concentrated to give 22 mg of t-butyl 4-[7-(2-butynyl)-2-(1-carboxycyclopropyloxy)-1-methyl-6-oxo-6,7-dihydro-1H-purin-8-yl]piperazine-1-carboxylate. 11 mg of this compound was dissolved in trifluoroacetic acid, and the mixture was concentrated. The residue was purified by reverse-phase high performance liquid chromatography (using an acetonitrile-water mobile phase (containing 0.1% trifluoroacetic acid)) to give 1.64 mg of the title compound.

Quelle