反应详情

温度

0 °C

A solution of cyclobutanecarboxylic acid [(3-benzyloxy-phenyl)-(5-oxo-4,5-dihydro-[1,2,4]triazin-6-yl)-methyl]-amide (216 mg, 0.553 mmol) in POCl3 (5 mL) was heated to 55° C. in an oil bath for 3 h. The reaction mixture was concentrated in vacuo and cooled to 0° C. and charged with 2M NH3 in i-PrOH until slightly basic. The solution was concentrated in vacuo and the reaction mixture was partitioned between EtOAc and H2O and separated. The aqueous layer was re-extracted with EtOAc (3×) and the combined EtOAc fractions were dried over Na2SO4, filtered and concentrated in vacuo to obtain the title compound as an off-white foam solid with no further purification. 1H NMR (CDCl3, 400 MHz) δ 1.98-2.07 (m, 1H), 2.08-2.21 (m, 1H), 2.36-2.48 (m, 2H), 2.62-2.77 (m, 2H), 4.09 (quint, J=8.8 Hz, 1H), 5.13 (s, 2H), 6.98 (dd, J=2.0, 7.2 Hz, 1H), 7.27-7.7.40 (m, 4H), 7.42-7.49 (m, 3H), 7.88 (d, J=8.0 Hz, 1H), 7.99 (brs, 1H); MS(ES+): m/z 373.1 (100) [MH+]; HPLC: tR=3.25 min (MicromassZQ, nonpolar—5 min).

1. concentrationThe reaction mixture was concentrated in vacuo
2. additioncharged with 2M NH3 in i-PrOH until slightly basic
3. concentrationThe solution was concentrated in vacuo
4. customthe reaction mixture was partitioned between EtOAc and H2O
5. customseparated
6. extractionThe aqueous layer was re-extracted with EtOAc (3×)
7. dry with materialthe combined EtOAc fractions were dried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated in vacuo