Reaktion #659224

Reaktionsgleichung

(8S,9aR)-8-[(5-Cyclopropylpyrazin-2-yl)oxy]octahydro-5H-pyrrolo[1,2-a][1,4]diazepin-5-one hydrochloride

2-Chloro-5-(trifluoromethyl)pyridine

sodium carbonate

→

titled compound

Ausbeute 40.0%

(8S,9aR)-8-[(5-cyclopropylpyrazin-2-yl)oxy]-2-[5-(trifluoromethyl)pyridin-2-yl]octahydro-5H-pyrrolo[1,2-a][1,4]diazepin-5-one

Ausbeute 40.0%

Lösungsmittel

dimethyl sulfoxide

ethyl acetate

ethyl acetate

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe reaction was cooled to room temperature
2. 2
   Waschenwashed with water and brine
3. 3
   Trocknendried over sodium sulfate
4. 4
   SonstigeThe solvent was removed in vacuo
5. 5
   Sonstigethe residue was purified via silica chromatography on 2 sequentially linked 4 g silica cartridges
6. 6
   Wascheneluting with 25:75 to 0:100 heptanes

Vorschrift

(8S,9aR)-8-[(5-Cyclopropylpyrazin-2-yl)oxy]octahydro-5H-pyrrolo[1,2-a][1,4]diazepin-5-one hydrochloride was dissolved in dimethyl sulfoxide (1.0 mL). 2-Chloro-5-(trifluoromethyl)pyridine (28.0 mg, 0.154 mmol, 1.5 equivalents) and sodium carbonate (65.5 mg, 0.618 mmol, 6.0 equivalents) were added, and the resulting suspension was heated to 115° C. for 14 hours. The reaction was cooled to room temperature, diluted with ethyl acetate, and washed with water and brine, and then dried over sodium sulfate. The solvent was removed in vacuo, and the residue was purified via silica chromatography on 2 sequentially linked 4 g silica cartridges, eluting with 25:75 to 0:100 heptanes:ethyl acetate to give the titled compound (16 mg, 40% yield) as a white solid. 1H NMR (300 MHz, CDCl3) δ ppm 8.42 (s, 1H), 7.96 (dd, J=14.0, 1.2 Hz, 2H), 7.67 (dd, J=9.0, 2.4 Hz, 1H), 6.66 (d, J=9.0 Hz, 1H), 5.48 (t, J=4.0 Hz, 1H), 4.81 (d, J=14.6 Hz, 1H), 4.37-4.32 (m, 1H), 4.19-4.10 (m, 1H), 4.04 (dd, J=13.9, 2.2 Hz, 1H), 3.73 (dd, J=13.8, 4.1 Hz, 1H), 3.54-3.36 (m, 1H), 3.04 (dd, J=14.5, 9.4 Hz, 1H), 2.75 (dd, J=6.6, 3.6 Hz, 2H), 2.55 (dd, J=13.8, 5.1 Hz, 1H), 2.05-1.95 (m, 2H), 0.98-0.91 (m, 4H); 1H NMR (400 MHz, pyridine-d5) δ ppm 8.63 (s, 1H), 8.16 (d, J=1.1 Hz, 1H), 8.08 (d, J=1.2 Hz, 1H), 7.79 (dd, J=9.0, 2.4 Hz, 1H), 6.90 (d, J=9.1 Hz, 1H), 5.52 (t, J=4.0 Hz, 1H), 4.82 (d, J=14.5 Hz, 1H), 4.53-4.24 (m, 3H), 3.92 (dd, J=13.6, 4.1 Hz, 1H), 3.40 (ddd, J=14.7, 10.2, 1.9 Hz, 1H), 3.07 (dd, J=14.5, 9.4 Hz, 1H), 2.89-2.72 (m, 2H), 2.65-2.47 (m, 1H), 2.11-1.91 (m, 2H), 1.10-0.97 (m, 2H), 0.97-0.81 (m, 2H); MS (ESI+) m/z 434.1 (M+H)+; [α]D24.8=−3.2 (c=0.41, CH3OH).

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