iodomethylcyclopropane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 464 mg (1.24 mmol) of tert-butyl [4-(5-chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]acetate and 293 mg (1.61 mmol) of (iodomethyl)cyclopropane were reacted according to General Method 7A. Yield: 379 mg (71% of theory)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The titled compound was prepared using similar procedure as that of Example-1 (step-2) using product of step 1 described above and ethyl 2-(hydroxyamino)benzoate in 50% yield.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The titled compound was prepared using similar procedure as that of Example-1 (step-2) using product of step 1 described above and ethyl 2-(hydroxyamino)benzoate in 50% yield.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of (E)-N-(2-(6-bromobenzo[d]isoxazol-3-yl)benzylidene)-1,1-bis(4-fluorophenyl)methanamine (Compound 8) (1.34 g) in dry tetrahydrofuran (15 mL) under nitrogen was cooled to −78° C. with stirring and a 1M solution of potassium tert-butoxide in tetrahydrofuran (3.2 mL) added dropwise. Solution turned dark purple. After 20 min (iodomethyl)cyclopropane (1.45 g) was added in one portion and solution slowly warmed to room temperature, stirred at this temperature for 1.5 h then quenched by the addition of water (10 mL) and extracted with ethyl acetate. The organic extract was dried over anhydrous magnesium sulfate and evaporated to leave a dark red gum that was dissolved in acetone (20 mL) and an aqueous 2N HCl solution (15 mL) added and the mixture stirred overnight. The acetone was removed by evaporation and the aqueous solution extracted with dichloromethane. The aqueous solution was made basic with sodium bicarbonate and extracted with dichloromethane, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. SCX purification (eluting with methanol then ammonia in methanol) followed by flash chromatography on silica eluting with 0 to 5% methanol in dichloromethane gave the title product (0.39 g). stirred at this temperature for 1.5 h then quenched by the addition of water (10 mL) extracted with ethyl acetate The organic extract was dried over anhydrous magnesium sulfate evaporated to leave a dark red gum that the mixture stirred overnight The acetone was removed by evaporation the aqueous solution extracted with dichloromethane extracted with dichloromethane dried over anhydrous magnesium sulfate evaporated under reduced pressure SCX purification ( eluting with methanol

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of (E)-N-(2-(6-bromobenzo[d]isoxazol-3-yl)benzylidene)-1,1-bis(4-fluorophenyl)methanamine (Compound 8) (1.34 g) in dry tetrahydrofuran (15 mL) under nitrogen was cooled to −78° C. with stirring and a 1M solution of potassium tert-butoxide in tetrahydrofuran (3.2 mL) added dropwise. Solution turned dark purple. After 20 min (iodomethyl)cyclopropane (1.45 g) was added in one portion and solution slowly warmed to room temperature, stirred at this temperature for 1.5 h then quenched by the addition of water (10 mL) and extracted with ethyl acetate. The organic extract was dried over anhydrous magnesium sulfate and evaporated to leave a dark red gum that was dissolved in acetone (20 mL) and an aqueous 2N HCl solution (15 mL) added and the mixture stirred overnight. The acetone was removed by evaporation and the aqueous solution extracted with dichloromethane. The aqueous solution was made basic with sodium bicarbonate and extracted with dichloromethane, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. SCX purification (eluting with methanol then ammonia in methanol) followed by flash chromatography on silica eluting with 0 to 5% methanol in dichloromethane gave the title product (0.39 g). stirred at this temperature for 1.5 h then quenched by the addition of water (10 mL) extracted with ethyl acetate The organic extract was dried over anhydrous magnesium sulfate evaporated to leave a dark red gum that the mixture stirred overnight The acetone was removed by evaporation the aqueous solution extracted with dichloromethane extracted with dichloromethane dried over anhydrous magnesium sulfate evaporated under reduced pressure SCX purification ( eluting with methanol

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 464 mg (1.24 mmol) of tert-butyl [4-(5-chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]acetate and 293 mg (1.61 mmol) of (iodomethyl)cyclopropane were reacted according to General Method 7A. Yield: 379 mg (71% of theory)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 349 mg (0.91 mmol) of tert-butyl [5-chloro-4-(5-chloro-2-cyanophenyl)-2-oxopyridin-1(2H)-yl]acetate and 216 mg (1.18 mmol) of (iodomethyl)cyclopropane were reacted according to General Method 7A. Yield: 245 mg (62% of theory)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 464 mg (1.24 mmol) of tert-butyl [4-(5-chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]acetate and 293 mg (1.61 mmol) of (iodomethyl)cyclopropane were reacted according to General Method 7A. Yield: 379 mg (71% of theory)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 349 mg (0.91 mmol) of tert-butyl [5-chloro-4-(5-chloro-2-cyanophenyl)-2-oxopyridin-1(2H)-yl]acetate and 216 mg (1.18 mmol) of (iodomethyl)cyclopropane were reacted according to General Method 7A. Yield: 245 mg (62% of theory)

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of N′-hydroxy-N-{6-[({[(Z)-(4-methyl-5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)(phenyl)methylene]amino}oxy)methyl]pyridin-2-yl}ethanimidamide (150 mg, 0.392 mmol, 1 eq), iodomethylcyclopropane (0.069 ml, 0.588 mmol, 1.5 eq) and cesium carbonate (191 mg, 0.588 mmol, 1.5 eq) in DMF (3 ml) was stirred at 80° C. for 7 h and overnight at room temperature. Iodomethylcyclopropane (0.069 ml, 0.588 mmol, 1.5 eq), cesium carbonate (191 mg, 0.588 mmol, 1.5 eq) and potassium iodide (0.1 eq) were then added and the mixture was stirred at 60° C. for 8 h. Water was added and the mixture was extracted with ethyl acetate. The organics were combined, dried over MgSO4 and evaporated. The residue was purified by chromatography on silica gel to afford N′-(cyclopropylmethoxy)-N-{6-[({[(Z)-(4-methyl-5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)(phenyl)methylene]amino}oxy)methyl]pyridin-2-yl}ethanimidamide (20 mg, 10% yield) as a transparent oil. the mixture was extracted with ethyl acetate dried over MgSO4 evaporated The residue was purified by chromatography on silica gel

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The titled compound was prepared using similar procedure as that of Example-1 (step-2) using product of step 1 described above and ethyl 2-(hydroxyamino)benzoate in 50% yield.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of (E)-N-(2-(6-bromobenzo[d]isoxazol-3-yl)benzylidene)-1,1-bis(4-fluorophenyl)methanamine (Compound 8) (1.34 g) in dry tetrahydrofuran (15 mL) under nitrogen was cooled to −78° C. with stirring and a 1M solution of potassium tert-butoxide in tetrahydrofuran (3.2 mL) added dropwise. Solution turned dark purple. After 20 min (iodomethyl)cyclopropane (1.45 g) was added in one portion and solution slowly warmed to room temperature, stirred at this temperature for 1.5 h then quenched by the addition of water (10 mL) and extracted with ethyl acetate. The organic extract was dried over anhydrous magnesium sulfate and evaporated to leave a dark red gum that was dissolved in acetone (20 mL) and an aqueous 2N HCl solution (15 mL) added and the mixture stirred overnight. The acetone was removed by evaporation and the aqueous solution extracted with dichloromethane. The aqueous solution was made basic with sodium bicarbonate and extracted with dichloromethane, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. SCX purification (eluting with methanol then ammonia in methanol) followed by flash chromatography on silica eluting with 0 to 5% methanol in dichloromethane gave the title product (0.39 g). stirred at this temperature for 1.5 h then quenched by the addition of water (10 mL) extracted with ethyl acetate The organic extract was dried over anhydrous magnesium sulfate evaporated to leave a dark red gum that the mixture stirred overnight The acetone was removed by evaporation the aqueous solution extracted with dichloromethane extracted with dichloromethane dried over anhydrous magnesium sulfate evaporated under reduced pressure SCX purification ( eluting with methanol