反应详情

温度

150 °C

To a solution of (rac)-1-[6-(1-Methyl-1H-pyrazol-4-yl)-imidazo[1,2-b]pyridazin-3-yl]-1-[2-(2-trimethylsilanyl-ethoxymethyl)-2H-indazol-5-yl]-ethanol (Stage 195.1, 194 mg, 0.396 mmol) in acetic acid (2.2 mL) were added iodine (201 mg, 0.792 mmol) and H3PO2 (0.436 mL of a 50% aqueous solution, 3.96 mmol). The mixture was then heated to 150° C. for 30 min. After cooling down to rt, the acetic acid was removed in vacuo and the residue was diluted with water and 10% Na2CO3-solution. The precipitate was filtered and washed with water and dried under vacuum overnight to afford the racemate. The mixture was then separated with a Preparative HPLC on a Chiralpak ADOOSC-JF004 (2.5×20 cm) column with a flow of 80 mL/min of n-heptane:EtOH:MeOH 70:25:10 (v/v). Oven 20° C., detection 210 nm (tR 41.3 min) to afford the title compound as a pure enantiomere (tR 3.64 min (conditions 3), MH+=344, 1H-NMR in DMSO-d6: 12.90 (s, 1H); 8.29 (s, 1H); 8.03-7.95 (m, 3H); 7.71 (s, 1H); 7.66 (s, 1H); 7.44-7.33 (m, 3H); 4.73 (q, 1H); 3.87 (s, 3H); 1.77 (d, 3H)).

1. temperatureAfter cooling down to rt
2. customthe acetic acid was removed in vacuo
3. additionthe residue was diluted with water and 10% Na2CO3-solution
4. filtrationThe precipitate was filtered
5. washwashed with water
6. customdried under vacuum overnight
7. customto afford the racemate
8. customThe mixture was then separated with a Preparative HPLC on a Chiralpak ADOOSC-JF004 (2.5×20 cm) column with a flow of 80 mL/min of n-heptane:EtOH:MeOH 70:25:10 (v/v)