Reaktion #7762

Reaktionsgleichung

morpholine-4-carboxylic acid 1-[2-(4-fluorophenyl)acetyl]-2-(2-phenoxypyrimidine-4-carbonyl)-pyrazolidin-4-yl ester

sodium hydride

→

desired product

Ausbeute 32.0%

morpholine-4-carboxylic acid 6-(4-fluorophenyl)-5-oxo-7-(2-phenoxypyrimidin-4-yl)-2,3-dihydro-1H,5H-pyrazolo[1,2-a]pyrazol-2-yl ester

Ausbeute 32.0%

Lösungsmittel

dimethylformamide

tetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe orange-colored solution is then quenched by slowly adding saturated NH4Cl (400 μL)
2. 2
   SonstigeThe cooling bath is removed
3. 3
   Temperaturto warm to room temperature
4. 4
   EinengenThe reaction mixture is concentrated in vacuo
5. 5
   workup.DISSOLUTIONthe resulting residue is dissolved in THF (25 mL)
6. 6
   Filtrationfiltered through a pad of Celite
7. 7
   EinengenThe filtrate is concentrated in vacuo
8. 8
   Sonstigethe residue purified by Prep HPLC

Vorschrift

A solution of morpholine-4-carboxylic acid 1-[2-(4-fluorophenyl)acetyl]-2-(2-phenoxypyrimidine-4-carbonyl)-pyrazolidin-4-yl ester, 42, (154 mg, 0.287 mmol) in dimethylformamide (3 mL) is added dropwise to a −10° C. suspension of sodium hydride (16.4 mg of a 60% dispersion in mineral oil, 0.410 mmol) in tetrahydrofuran (3 mL). After 1 hour at −10° C., the reaction was warmed to 0° C. for 2 hours. The orange-colored solution is then quenched by slowly adding saturated NH4Cl (400 μL). The cooling bath is removed, and the solution allowed to warm to room temperature. The reaction mixture is concentrated in vacuo and the resulting residue is dissolved in THF (25 mL) and filtered through a pad of Celite. The filtrate is concentrated in vacuo and the residue purified by Prep HPLC to afford 47 mg (32% yield) of the desired product as a yellow solid. 1H NMR (300 MHz, CDCl3) δ 8.46 (d, J=4.9 Hz, 1H), 7.47–7.18 (m, 9H), 7.08 (t, J=8.7 Hz, 2H), 6.89 (d, J=4.9 Hz, 1H), 5.66 (m, 1H), 4.16 (m, 2H), 4.02 (d, J=12.9Hz, 1H), 3.87 (dd, J=12.9, 5.1 Hz, 1H), 3.79–3.30 (m, 8H); HRMS m/z calcd for C27H25FN5O5 (MH+) 518.1840, found 518.1815.

Quelle