2-cyano-N-propan-2-ylacetamide

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

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

Procedure: The procedure described in Example 99 was repeated using 1.83 g of 3,4-dihydroxy-5-nitrobenzaldehyde and 1.3 g of N-isopropylcyanoacetamide. Yield 1.46 g (50%), m.p. 243°-245° C.

Conditions: temp:135.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 2-methyl-3-oxobutanal sodium salt (2.73 g, 22.4 mmol, prepared according to Paine, John B et al., J. Heterocycl. Chem., 1987, 24, 351), 2-cyano-N-isopropylacetamide (2.17 g, 17.2 mmol, prepared according to Wuerthner, Frank et al., J. Amer, Chem. Soc., 2002, 32, 9431) in N,N-dimethylformamide (17.2 mL) were added piperidine (292 mg, 3.43 mmol) and acetic acid (1.34 g, 22.4 mmol) successively at room temperature, and the mixture was stirred at 135° C. for 7 h. After cooling, the mixture was quenched with water (100 mL), extracted with dichloromethane (50 mL×4). The combined organic layers were dried over magnesium sulfate and concentrated in vacuo. The residue was chromatographed on a column of silica gel eluting with n-hexane/ethyl acetate (v/v=2/1˜1/1) to give 840 mg (26%) of the title compound as an orange colored solid. After cooling the mixture was quenched with water (100 mL) extracted with dichloromethane (50 mL×4) The combined organic layers were dried over magnesium sulfate concentrated in vacuo The residue was chromatographed on a column of silica gel eluting with n-hexane/ethyl acetate (v/v=2/1˜1/1)

Conditions: temp:135.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 2-methyl-3-oxobutanal sodium salt (2.73 g, 22.4 mmol, prepared according to Paine, John B et al., J. Heterocycl. Chem., 1987, 24, 351), 2-cyano-N-isopropylacetamide (2.17 g, 17.2 mmol, prepared according to Wuerthner, Frank et al., J. Amer, Chem. Soc., 2002, 32, 9431) in N,N-dimethylformamide (17.2 mL) were added piperidine (292 mg, 3.43 mmol) and acetic acid (1.34 g, 22.4 mmol) successively at room temperature, and the mixture was stirred at 135° C. for 7 h. After cooling, the mixture was quenched with water (100 mL), extracted with dichloromethane (50 mL×4). The combined organic layers were dried over magnesium sulfate and concentrated in vacuo. The residue was chromatographed on a column of silica gel eluting with n-hexane/ethyl acetate (v/v=2/1˜1/1) to give 840 mg (26%) of the title compound as an orange colored solid. After cooling the mixture was quenched with water (100 mL) extracted with dichloromethane (50 mL×4) The combined organic layers were dried over magnesium sulfate concentrated in vacuo The residue was chromatographed on a column of silica gel eluting with n-hexane/ethyl acetate (v/v=2/1˜1/1)

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1.0 g (8.0 mmol) of 2-cyano-N-(1-methylethyl)acetamide (prepared according to the procedure of Cheikh et al J. Org. Chem., 1991, 56, 970) was combined with 3.1 mL of triethylorthoformate, 5 mL of acetic anhydride and 0.01 g of anhydrous zinc chloride. The mixture was refluxed for 1 hour. A distillation head was placed on the flask and the reaction was heated at 120° C. for 8 hours. After standing for two days the mixture was heated again for 12 hours at 120° C. for 12 hours. The volatiles were removed with a rotary evaporator. Ethanol was added and the volatiles were again removed with a rotary evaporator. This material was dissolved in 15 mL of ethanol. 0.34 mL (6.4 mmol) of methyl hydrazine was added. The reaction mixture was refluxed for 5 hours and then allowed to stand at room temperature overnight. The solvent was removed with a rotary evaporator. The residue was purified by MPLC (ethyl acetate as eluant) to afford 0.14 g of the title compound as a solid. The mixture was refluxed for 1 hour the mixture was heated again for 12 hours at 120° C. for 12 hours The volatiles were removed with a rotary evaporator Ethanol was added the volatiles were again removed with a rotary evaporator This material was dissolved in 15 mL of ethanol The reaction mixture was refluxed for 5 hours to stand at room temperature overnight The solvent was removed with a rotary evaporator The residue was purified by MPLC (ethyl acetate as eluant)

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1.0 g (8.0 mmol) of 2-cyano-N-(1-methylethyl)acetamide (prepared according to the procedure of Cheikh et al J. Org. Chem., 1991, 56, 970) was combined with 3.1 mL of triethylorthoformate, 5 mL of acetic anhydride and 0.01 g of anhydrous zinc chloride. The mixture was refluxed for 1 hour. A distillation head was placed on the flask and the reaction was heated at 120° C. for 8 hours. After standing for two days the mixture was heated again for 12 hours at 120° C. for 12 hours. The volatiles were removed with a rotary evaporator. Ethanol was added and the volatiles were again removed with a rotary evaporator. This material was dissolved in 15 mL of ethanol. 0.34 mL (6.4 mmol) of methyl hydrazine was added. The reaction mixture was refluxed for 5 hours and then allowed to stand at room temperature overnight. The solvent was removed with a rotary evaporator. The residue was purified by MPLC (ethyl acetate as eluant) to afford 0.14 g of the title compound as a solid. The mixture was refluxed for 1 hour the mixture was heated again for 12 hours at 120° C. for 12 hours The volatiles were removed with a rotary evaporator Ethanol was added the volatiles were again removed with a rotary evaporator This material was dissolved in 15 mL of ethanol The reaction mixture was refluxed for 5 hours to stand at room temperature overnight The solvent was removed with a rotary evaporator The residue was purified by MPLC (ethyl acetate as eluant)

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

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

Procedure: The procedure described in Example 99 was repeated using 1.83 g of 3,4-dihydroxy-5-nitrobenzaldehyde and 1.3 g of N-isopropylcyanoacetamide. Yield 1.46 g (50%), m.p. 243°-245° C.

Conditions: temp:135.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 2-methyl-3-oxobutanal sodium salt (2.73 g, 22.4 mmol, prepared according to Paine, John B et al., J. Heterocycl. Chem., 1987, 24, 351), 2-cyano-N-isopropylacetamide (2.17 g, 17.2 mmol, prepared according to Wuerthner, Frank et al., J. Amer, Chem. Soc., 2002, 32, 9431) in N,N-dimethylformamide (17.2 mL) were added piperidine (292 mg, 3.43 mmol) and acetic acid (1.34 g, 22.4 mmol) successively at room temperature, and the mixture was stirred at 135° C. for 7 h. After cooling, the mixture was quenched with water (100 mL), extracted with dichloromethane (50 mL×4). The combined organic layers were dried over magnesium sulfate and concentrated in vacuo. The residue was chromatographed on a column of silica gel eluting with n-hexane/ethyl acetate (v/v=2/1˜1/1) to give 840 mg (26%) of the title compound as an orange colored solid. After cooling the mixture was quenched with water (100 mL) extracted with dichloromethane (50 mL×4) The combined organic layers were dried over magnesium sulfate concentrated in vacuo The residue was chromatographed on a column of silica gel eluting with n-hexane/ethyl acetate (v/v=2/1˜1/1)

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

Procedure: The procedure described in Example 99 was repeated using 1.83 g of 3,4-dihydroxy-5-nitrobenzaldehyde and 1.3 g of N-isopropylcyanoacetamide. Yield 1.46 g (50%), m.p. 243°-245° C.

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

Procedure: The procedure described in Example 99 was repeated using 1.83 g of 3,4-dihydroxy-5-nitrobenzaldehyde and 1.3 g of N-isopropylcyanoacetamide. Yield 1.46 g (50%), m.p. 243-245° C.

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

Procedure: The procedure described in Example 99 was repeated using 1.83 g of 3,4-dihydroxy-5-nitrobenzaldehyde and 1.3 g of N-isopropylcyanoacetamide. Yield 1.46 g (50%), m.p. 243°-245° C.