[CH2:1]([O:3][C:4](=[O:18])[CH2:5][CH:6]1[O:10][B:9]([OH:11])[C:8]2[CH:12]=[C:13]([OH:17])[CH:14]=[C:15]([CH3:16])[C:7]1=2)[CH3:2].C(=O)([O-])[O-].[Cs+].[Cs+].[Cl:25][C:26]1[N:31]=[C:30](Cl)[CH:29]=[CH:28][N:27]=1>CN(C=O)C>[CH2:1]([O:3][C:4](=[O:18])[CH2:5][CH:6]1[O:10][B:9]([OH:11])[C:8]2[CH:12]=[C:13]([O:17][C:28]3[CH:29]=[CH:30][N:31]=[C:26]([Cl:25])[N:27]=3)[CH:14]=[C:15]([CH3:16])[C:7]1=2)[CH3:2]A solution of (1,6-dihydroxy-4-methyl-1,3-dihydro-benzo[c][1,2]oxaborol-3-yl)-acetic acid ethyl ester (3.30 g, 13.20 mmol) in DMF (10 mL) was treated with cesium carbonate (13.30 g, 40.82 mmol) at 0° C. followed by 2,4-dichloropyrimidine (3.90 g, 26.20 mmol). The mixture was stirred at room temperature for 24 hours. The suspension was quenched with ice water, acidified with 2N HCl and extracted with ethyl acetate. The extracts were dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by silica gel flash column chromatography (EtOAc/hexane; 1:1 then MeOH/CH2Cl2; 1:99 gradient) to give [6-(2-chloro-pyrimidin-4-yloxy)-1-hydroxy-4-methyl-1,3-dihydro-benzo[c][1,2]oxaborol-3-yl]-acetic acid ethyl ester as a yellow foam (3.00 g, 63%). 1H NMR (400 MHz, CD3OD) δ 8.48 (d, J=5.85 Hz, 1H), 7.22 (s, 1H), 7.10 (s, 1H), 6.98 (d, J=5.85 Hz, 1H), 5.65 (dd, J=8.20, 2.73 Hz, 1H), 4.14-4.07 (m, 2H), 3.18 (dd, J=15.22, 2.73 Hz, 1H), 2.52 (dd, J=15.22, 8.20 Hz, 1H), 2.39 (s, 3H), 1.19 (t, J=7.03 Hz, 3H).
Wird geladen…
