2-(2-methylpropoxymethyl)oxirane

反応条件: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 7,8-bis(4-chlorophenyl)-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one, (20 mg, 0.056 mmol), prepared as described in Example 1, in 0.6 mL of DMF was added glycidyl isobutyl ether (7.3 mg, 0.056 mmol), followed by K2CO3 (15.5 mg, 0.112 mmol). The mixture was heated at 85° C. After stirring overnight, the reaction was allowed to cool to RT The reaction mixture was filtered to remove excess of K2CO3. The collected solution was concentrated under reduced pressure. The crude product was purified using reverse phase HPLC to give the title compound, 3,4-bis(4-chlorophenyl)-6-(2-hydroxy-3-isobutoxypropyl)imidazo[1,5-b]pyridazin-7(6H)-one (17.8 mg, 65% yield) as a yellow solid. in 65% yield. MS [M+H]+: found 487; 1H NMR (CDCl3, 400 MHz) δ 8.08 (s, 1H), 7.23-7.15 (m, 6H), 7.00-6.96 (m, 2H), 4.20-4.00 (m, 3H), 3.41 (d, 2H), 3.11 (d, 2H), 1.80-1.65 (m, 1H), 0.76 (d, 6H). to cool to RT The reaction mixture was filtered to remove excess of K2CO3 The collected solution was concentrated under reduced pressure The crude product was purified

反応条件: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 7,8-bis(4-chlorophenyl)-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one, (20 mg, 0.056 mmol), prepared as described in Example 1, in 0.6 mL of DMF was added glycidyl isobutyl ether (7.3 mg, 0.056 mmol), followed by K2CO3 (15.5 mg, 0.112 mmol). The mixture was heated at 85° C. After stirring overnight, the reaction was allowed to cool to RT The reaction mixture was filtered to remove excess of K2CO3. The collected solution was concentrated under reduced pressure. The crude product was purified using reverse phase HPLC to give the title compound, 3,4-bis(4-chlorophenyl)-6-(2-hydroxy-3-isobutoxypropyl)imidazo[1,5-b]pyridazin-7(6H)-one (17.8 mg, 65% yield) as a yellow solid. in 65% yield. MS [M+H]+: found 487; 1H NMR (CDCl3, 400 MHz) δ 8.08 (s, 1H), 7.23-7.15 (m, 6H), 7.00-6.96 (m, 2H), 4.20-4.00 (m, 3H), 3.41 (d, 2H), 3.11 (d, 2H), 1.80-1.65 (m, 1H), 0.76 (d, 6H). to cool to RT The reaction mixture was filtered to remove excess of K2CO3 The collected solution was concentrated under reduced pressure The crude product was purified

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 20 g. 1-(2-Methylpropoxy)-2,3-epoxypropane are dissolved in 40 ml. ethanol and the solution is warmed to 55° C. Subsequently, in the course of an hour and while stirring, there is added dropwise a solution of 13 g. pyrrolidine in 25 ml. ethanol. The temperature should thereby not increase above 70° C. After completion of the addition, stirring is continued for 1 hour at 70° C., the reaction mixture is then evaporated and the residue is distilled in a vacuum. There are obtained 35 g. 3-(2-methylpropoxy)-1-pyrrolidinopropan-2-ol; b.p. 134° C./14 mm.Hg. there is added dropwise a solution of 13 g The temperature should thereby not increase above 70° C After completion of the addition stirring the reaction mixture is then evaporated the residue is distilled in a vacuum There are obtained 35 g

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Compound 174 was synthesized using spiro[naphtho[1,2-b][1,4]oxathiine-2,4′-piperidine]-5,6-dione, 2-(isobutoxymethyl)oxirane and conditions outlined in procedure X. LCMS: 432 [M+H]; Rt=0.97 min.