1,2-oxazolidine

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: The sub-title compound was prepared by the method of example 21 step b) using the product of example 21 step a) and isoxazolidine.

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

実験手順: Procedure for the N-alkylation of S2: To a solution of isoxazolidine S1 (2.29 g, 11.49 mmol, 1 eq) in THF (109 mL) were added DMAP (0.07 g, 0.58 mmol, 0.05 eq), Et3N (2.24 mL, 16.09 mmol, 1.4 eq), and TBSOTf (3.70 mL, 16.09 mmol, 1.4 eq) to protect the primary alcohol in 97% yield following purification by flash chromatography (9:1 hexanes/EtOAc). To a solution of TBS-protected isoxazolidine S2 (0.17 g, 0.53 mmol, 1 eq) in DMF (2 mL) was added i-Pr2NEt (0.28 mL, 1.59 mmol, 3 eq) and BnBr or tert-butylbromoacetate (2.64 mmol, 5 eq). The reaction mixture was irradiated in a 1000 W microwave (5×15 s) @ 30% power with mixing between each interval. Once the reaction was complete by TLC analysis, the reaction was diluted with H2O (15 mL), and extracted with Et2O (3×15 mL). The combined organic extracts were washed with H2O (1×20 mL), brine (1×20 mL), dried over Na2SO4, filtered, and concentrated in vacuo. purification by flash chromatography (9:1 hexanes/EtOAc) The reaction mixture was irradiated in a 1000 W microwave (5×15 s) with mixing between each interval extracted with Et2O (3×15 mL) The combined organic extracts were washed with H2O (1×20 mL), brine (1×20 mL) dried over Na2SO4 filtered concentrated in vacuo

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

実験手順: Procedure for the N-alkylation of S2: To a solution of isoxazolidine S1 (2.29 g, 11.49 mmol, 1 eq) in THF (109 mL) were added DMAP (0.07 g, 0.58 mmol, 0.05 eq), Et3N (2.24 mL, 16.09 mmol, 1.4 eq), and TBSOTf (3.70 mL, 16.09 mmol, 1.4 eq) to protect the primary alcohol in 97% yield following purification by flash chromatography (9:1 hexanes/EtOAc). To a solution of TBS-protected isoxazolidine S2 (0.17 g, 0.53 mmol, 1 eq) in DMF (2 mL) was added i-Pr2NEt (0.28 mL, 1.59 mmol, 3 eq) and BnBr or tert-butylbromoacetate (2.64 mmol, 5 eq). The reaction mixture was irradiated in a 1000 W microwave (5×15 s) @ 30% power with mixing between each interval. Once the reaction was complete by TLC analysis, the reaction was diluted with H2O (15 mL), and extracted with Et2O (3×15 mL). The combined organic extracts were washed with H2O (1×20 mL), brine (1×20 mL), dried over Na2SO4, filtered, and concentrated in vacuo. purification by flash chromatography (9:1 hexanes/EtOAc) The reaction mixture was irradiated in a 1000 W microwave (5×15 s) with mixing between each interval extracted with Et2O (3×15 mL) The combined organic extracts were washed with H2O (1×20 mL), brine (1×20 mL) dried over Na2SO4 filtered concentrated in vacuo

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a cold (0° C.) solution of chlorosulfonyl isocyanate (0.437 mL, 5.02 mmol) in CH2Cl2 (10 mL) was added tert-BuOH (0.480 mL, 5.02 mmol) and the mixture was stirred for 1 h at 0° C. Then HCl salt of isoxazolidine (0.5 g, 4.56 mmol) and TEA (1.399 mL, 10.04 mmol) were added consecutively and the mixture was stirred overnight. Rxn was diluted with EtOAc and washed with ice cold 1N HCl, brine and then dried (MgSO4). Isolated crude product was purified by Biotage 25M column to afford tert-butyl isoxazolidin-2-ylsulfonylcarbamate as a beige solid (0.82 g, 71%). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.50 (9 H, s), 2.38 (2 H, quin, J=7.37 Hz), 3.81 (2 H, m), 4.19 (2 H, t, J=7.30 Hz). To a cold (0-5° C.) solution of tert-butyl isoxazolidin-2-ylsulfonylcarbamate (0.82 g, 3.25 mmol) in DCM (2 mL) was added TFA (2 mL, 35.1 mmol) and the reaction mixture was stirred for 2 h at r.t and removed the solvent to afford isoxazolidine-2-sulfonamide (0.229 g, 46%). 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 2.40 (2 H, quin, J=7.32 Hz), 3.65 (2 H, m), 4.20 (2 H, t, J=7.32 Hz), 4.83 (2 H, brs). the mixture was stirred overnight washed with ice cold 1N HCl, brine dried (MgSO4) Isolated crude product was purified by Biotage 25M column

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a cold (0° C.) solution of chlorosulfonyl isocyanate (0.437 mL, 5.02 mmol) in CH2Cl2 (10 mL) was added tert-BuOH (0.480 mL, 5.02 mmol) and the mixture was stirred for 1 h at 0° C. Then HCl salt of isoxazolidine (0.5 g, 4.56 mmol) and TEA (1.399 mL, 10.04 mmol) were added consecutively and the mixture was stirred overnight. Rxn was diluted with EtOAc and washed with ice cold 1N HCl, brine and then dried (MgSO4). Isolated crude product was purified by Biotage 25M column to afford tert-butyl isoxazolidin-2-ylsulfonylcarbamate as a beige solid (0.82 g, 71%). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.50 (9 H, s), 2.38 (2 H, quin, J=7.37 Hz), 3.81 (2 H, m), 4.19 (2 H, t, J=7.30 Hz). To a cold (0-5° C.) solution of tert-butyl isoxazolidin-2-ylsulfonylcarbamate (0.82 g, 3.25 mmol) in DCM (2 mL) was added TFA (2 mL, 35.1 mmol) and the reaction mixture was stirred for 2 h at r.t and removed the solvent to afford isoxazolidine-2-sulfonamide (0.229 g, 46%). 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 2.40 (2 H, quin, J=7.32 Hz), 3.65 (2 H, m), 4.20 (2 H, t, J=7.32 Hz), 4.83 (2 H, brs). the mixture was stirred overnight washed with ice cold 1N HCl, brine dried (MgSO4) Isolated crude product was purified by Biotage 25M column

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

実験手順: The sub-title compound was prepared by the method of example 21 step b) using the product of example 21 step a) and isoxazolidine.

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

実験手順: The sub-title compound was prepared by the method of example 21 step b) using the product of example 21 step a) and isoxazolidine.

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

実験手順: 5-[1-(4-Chloro-2-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-2-isoxazolidin-2-yl-thiazol-4-one was prepared from 5-[1-(4-Chloro-2-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-2-ethylsulfanyl-thiazol-4-one and isoxazolidine following General Procedure B.

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

実験手順: 5-[1-(4-Chloro-2-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-2-isoxazolidin-2-yl-thiazol-4-one was prepared from 5-[1-(4-Chloro-2-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-2-ethylsulfanyl-thiazol-4-one and isoxazolidine following General Procedure B.

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

実験手順: 1,4-dioxaspiro[4.5]decan-8-one (358.5 mg, 2.3 mmol), and isoxazolidine (168 mg, 2.3 mmol), and sodium triacetoxyborohydride (1.46 g, 6.9 mmol) were taken in acetonitrile and stirred for 18 h at room temperature. The mixture concentrated under vacuum and the residue basified with NaHCO3, saturated with solid NaCl and extracted with EtOAc/iPrOH (4:1) four times. Organic layer separated, dried over Na2SO4 and evaporated. Residue purified by silica column chromatography to give the title compound. The mixture concentrated under vacuum extracted with EtOAc/iPrOH (4:1) four times Organic layer separated dried over Na2SO4 evaporated Residue purified by silica column chromatography