3-cyclopropyl-3-oxopropanenitrile

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 126a (477 mg, 4.38 mmol) in methanol (5 mL) was added hydrazine hydrate (5 mL, 80%). The reaction mixture was heated at 75° C. for 15 h. The methanol was removed under reduced pressure and the residue was extracted with dichloromethane (2×8 mL). The combined extract was dried over Na2SO4 and concentrated. The residue was purified by flash column eluting with 100:1 dichloromethane/methanol to afford 126b as a yellow oil (250 mg, 46%, over two steps). MS: [M+H]+ 124. The methanol was removed under reduced pressure the residue was extracted with dichloromethane (2×8 mL) The combined extract was dried over Na2SO4 concentrated The residue was purified by flash column eluting with 100:1 dichloromethane/methanol

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

Procedure: 5 g (0.046 mol) of 3cyclopropyl-3-oxo-propanenitrile were dissolved in 200 ml of ethanol and 2.26 ml (0.046 mol) of hydrazine hydrate were added. The solution was maintained at reflux for 5 hours and then the solvent evaporated under vacuum. The residue was re-dissolved with methylene chloride and washed several times with brine. The organic layer was dried over anhydrous sodium sulfate and the solvent evaporated to give 4.53 g (80% yield) of the title compound. The solution was maintained at reflux for 5 hours the solvent evaporated under vacuum The residue was re-dissolved with methylene chloride washed several times with brine The organic layer was dried over anhydrous sodium sulfate the solvent evaporated

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

Procedure: To a solution of 2.61 g (24.0 mmol) 3-cyclopropyl-3-oxopropanenitrile in 150 mL DMSO was added 1.01 g (25.2 mmol) 60% NaH in oil. After 1 hour, 3.50 g (12.0 mmol) 4'-bromomethyl-2-nitrobiphenyl was added all at once to the solution. After 3 hours, the solution was poured into brine and extracted 3 times with ether. The combined organic material was dried over MgSO4, stripped of solvent in vacuo, and was chromatographed on silica gel under medium pressure using 3/40/57 EtOAc/CH2Cl2/hexanes to give 1.29 g (34% yield) of the title compound as a yellow glass. Rf 0.13 in 3/40/57 EtOAc/CH2Cl2/hexanes, visualized by UV and ammonium molybdate/ceric sulfate stain; Rf of the dialkylated material is 0.19 in the same solvent mixture. After 3 hours extracted 3 times with ether The combined organic material was dried over MgSO4 was chromatographed on silica gel under medium pressure

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

Procedure: To a solution of 2.61 g (24.0 mmol) 3-cyclopropyl-3-oxopropanenitrile in 150 mL DMSO was added 1.01 g (25.2 mmol) 60% NaH in oil. After 1 hour, 3.50 g (12.0 mmol) 4'-bromomethyl-2-nitrobiphenyl was added all at once to the solution. After 3 hours, the solution was poured into brine and extracted 3 times with ether. The combined organic material was dried over MgSO4, stripped of solvent in vacuo, and was chromatographed on silica gel under medium pressure using 3/40/57 EtOAc/CH2Cl2/hexanes to give 1.29 g (34% yield) of the title compound as a yellow glass. Rf 0.13 in 3/40/57 EtOAc/CH2Cl2/hexanes, visualized by UV and ammonium molybdate/ceric sulfate stain; Rf of the dialkylated material is 0.19 in the same solvent mixture. After 3 hours extracted 3 times with ether The combined organic material was dried over MgSO4 was chromatographed on silica gel under medium pressure

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

Procedure: A THF (2 ml) suspension of sodium hydride (0.06 g, 60% oil suspension, 18.78 mmol) was cooled in an ice bath, and a THF (2 ml) solution of 3-cyclopropyl-3-oxopropanenitrile was dripped thereto. To the obtained reaction solution, a THF (3 ml) solution of 2-methyl-6-(1H-1,2,4-triazol-1-yl) nicotinic acid chloride (0.16 g, 0.73 mmol) was dripped. The resultant was stirred at room temperature for 3 hours. The obtained reaction solution was made acidic with a citric acid aqueous solution, and the product was extracted with ethyl acetate. The obtained organic layer was washed with water, dried with magnesium sulfate and concentrated to obtain the desired product (0.14 g, yield 64%). was cooled in an ice bath To the obtained reaction solution The obtained reaction solution the product was extracted with ethyl acetate The obtained organic layer was washed with water dried with magnesium sulfate concentrated

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

Procedure: A THF (2 ml) suspension of sodium hydride (0.06 g, 60% oil suspension, 18.78 mmol) was cooled in an ice bath, and a THF (2 ml) solution of 3-cyclopropyl-3-oxopropanenitrile was dripped thereto. To the obtained reaction solution, a THF (3 ml) solution of 2-methyl-6-(1H-1,2,4-triazol-1-yl) nicotinic acid chloride (0.16 g, 0.73 mmol) was dripped. The resultant was stirred at room temperature for 3 hours. The obtained reaction solution was made acidic with a citric acid aqueous solution, and the product was extracted with ethyl acetate. The obtained organic layer was washed with water, dried with magnesium sulfate and concentrated to obtain the desired product (0.14 g, yield 64%). was cooled in an ice bath To the obtained reaction solution The obtained reaction solution the product was extracted with ethyl acetate The obtained organic layer was washed with water dried with magnesium sulfate concentrated

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

Procedure: When β-cyclopropyl-β-oxopropionitrile (2,.00 g, 18.3 mmoles) [prepared in Example 1, Step A]was reacted with allylisocyanate (1.60 g, 19.2 mmoles) according to the general procedure of Example 1, Sep B, the title compound (2.8 g) was obtained as a white solid after recrystallization from 30% aqueous ethanol, m.p. 72°-73.5° C.

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

Procedure: When β-cyclopropyl-β-oxopropionitrile (2,.00 g, 18.3 mmoles) [prepared in Example 1, Step A]was reacted with allylisocyanate (1.60 g, 19.2 mmoles) according to the general procedure of Example 1, Sep B, the title compound (2.8 g) was obtained as a white solid after recrystallization from 30% aqueous ethanol, m.p. 72°-73.5° C.

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 126a (477 mg, 4.38 mmol) in methanol (5 mL) was added hydrazine hydrate (5 mL, 80%). The reaction mixture was heated at 75° C. for 15 h. The methanol was removed under reduced pressure and the residue was extracted with dichloromethane (2×8 mL). The combined extract was dried over Na2SO4 and concentrated. The residue was purified by flash column eluting with 100:1 dichloromethane/methanol to afford 126b as a yellow oil (250 mg, 46%, over two steps). MS: [M+H]+ 124. The methanol was removed under reduced pressure the residue was extracted with dichloromethane (2×8 mL) The combined extract was dried over Na2SO4 concentrated The residue was purified by flash column eluting with 100:1 dichloromethane/methanol

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 126a (477 mg, 4.38 mmol) in methanol (5 mL) was added hydrazine hydrate (5 mL, 80%). The reaction mixture was heated at 75° C. for 15 h. The methanol was removed under reduced pressure and the residue was extracted with dichloromethane (2×8 mL). The combined extract was dried over Na2SO4 and concentrated. The residue was purified by flash column eluting with 100:1 dichloromethane/methanol to afford 126b as a yellow oil (250 mg, 46%, over two steps). MS: [M+H]+ 124. The methanol was removed under reduced pressure the residue was extracted with dichloromethane (2×8 mL) The combined extract was dried over Na2SO4 concentrated The residue was purified by flash column eluting with 100:1 dichloromethane/methanol

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

Procedure: 5 g (0.046 mol) of 3cyclopropyl-3-oxo-propanenitrile were dissolved in 200 ml of ethanol and 2.26 ml (0.046 mol) of hydrazine hydrate were added. The solution was maintained at reflux for 5 hours and then the solvent evaporated under vacuum. The residue was re-dissolved with methylene chloride and washed several times with brine. The organic layer was dried over anhydrous sodium sulfate and the solvent evaporated to give 4.53 g (80% yield) of the title compound. The solution was maintained at reflux for 5 hours the solvent evaporated under vacuum The residue was re-dissolved with methylene chloride washed several times with brine The organic layer was dried over anhydrous sodium sulfate the solvent evaporated