ethyl 2-cyano-2-(1,3-dioxolan-2-ylidene)acetate

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

Procedure: A stirred solution of cyano-[1,3]dioxolan-2-ylidene-acetic acid ethyl ester (prepared as described by Neidlein and Kikelj, Synthesis, 1988, 981, 266 mg, 1.45 mmol, 1.0 eq), N-cyclopropyl-3-hydrazino-4-methyl-benzamide trifluoroacetate (Example 6C, 463 mg, 1.45 mmol, 1.0 eq), and triethylamine (405 μL, 2.9 mmol, 2.0 eq) in 20 mL of ethanol was heated to 65° C. overnight. After cooling to room temperature, the mixture was concentrated and the residue purified by flash chromatography on silica gel (eluted with 1/1 hexanes/EtOAc followed by 100% EtOAc) to provide the desired compound as a tan solid (350 mg, 62%). HPLC (4 minute 10-95 gradient) tR 1.59 min; MS m/z 389.06 [M+H]+; 1H NMR (CD3OD), δ 7.87 (d, J=7.9 Hz, 1 H), 7.78 (s, 1 H), 7.49 (d, J=7.8 Hz, 1 H), 4.29 (dd, J=14.9, 6.9 Hz, 2 H), 4.19 (d, J=4.3 Hz, 2 H), 3.84 (d, J=4.4 Hz, 2 H), 2.84 (m, 1 H), 2.22 (s, 3 H), 1.35 (t, J=7.3 Hz, 3 H), 0.81 (d, J=5.3 Hz, 2 H), 0.63 (s, 2 H) ppm. the mixture was concentrated the residue purified by flash chromatography on silica gel (eluted with 1/1 hexanes/EtOAc followed by 100% EtOAc)

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

Procedure: A stirred solution of cyano-[1,3]dioxolan-2-ylidene-acetic acid ethyl ester (prepared as described by Neidlein and Kikelj, Synthesis, 1988, 981, 266 mg, 1.45 mmol, 1.0 eq), N-cyclopropyl-3-hydrazino-4-methyl-benzamide trifluoroacetate (Example 6C, 463 mg, 1.45 mmol, 1.0 eq), and triethylamine (405 μL, 2.9 mmol, 2.0 eq) in 20 mL of ethanol was heated to 65° C. overnight. After cooling to room temperature, the mixture was concentrated and the residue purified by flash chromatography on silica gel (eluted with 1/1 hexanes/EtOAc followed by 100% EtOAc) to provide the desired compound as a tan solid (350 mg, 62%). HPLC (4 minute 10-95 gradient) tR 1.59 min; MS m/z 389.06 [M+H]+; 1H NMR (CD3OD), δ 7.87 (d, J=7.9 Hz, 1 H), 7.78 (s, 1 H), 7.49 (d, J=7.8 Hz, 1 H), 4.29 (dd, J=14.9, 6.9 Hz, 2 H), 4.19 (d, J=4.3 Hz, 2 H), 3.84 (d, J=4.4 Hz, 2 H), 2.84 (m, 1 H), 2.22 (s, 3 H), 1.35 (t, J=7.3 Hz, 3 H), 0.81 (d, J=5.3 Hz, 2 H), 0.63 (s, 2 H) ppm. the mixture was concentrated the residue purified by flash chromatography on silica gel (eluted with 1/1 hexanes/EtOAc followed by 100% EtOAc)

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

Procedure: A stirred solution of cyano-[1,3]dioxolan-2-ylidene-acetic acid ethyl ester (prepared as described by Neidlein and Kikelj, Synthesis, 1988, 981, 266 mg, 1.45 mmol, 1.0 eq), N-cyclopropyl-3-hydrazino-4-methyl-benzamide trifluoroacetate (Example 6 C, 463 mg, 1.45 mmol, 1.0 eq), and triethylamine (405 μL, 2.9 mmol, 2.0 eq) in 20 mL of ethanol was heated to 65° C. overnight. After cooling to room temperature, the mixture was concentrated and the residue purified by flash chromatography on silica gel (eluted with 1/1 hexanes/EtOAc followed by 100% EtOAc) to provide the desired compound as a tan solid (350 mg, 62%). HPLC (4 minute 10-95 gradient) tR 1.59 min; MS ink 389.06 [M+H]+; 1H NMR (CD3OD), δ 7.87 (d, J=7.9 Hz, 1 H), 7.78 (s, 1 H), 7.49 (d, J=7.8 Hz, 1 H), 4.29 (dd, J=14.9, 6.9 Hz, 2 H), 4.19 (d, J=4.3 Hz, 2 H), 3.84 (d, J=4.4 Hz, 2 H), 2.84 (m, 1 H), 2.22 (s, 3 H), 1.35 (t, J=7.3 Hz, 3 H), 0.81 (d, J=5.3 Hz, 2 H), 0.63 (s, 2 H) ppm. the mixture was concentrated the residue purified by flash chromatography on silica gel (eluted with 1/1 hexanes/EtOAc followed by 100% EtOAc)

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

Procedure: A stirred solution of cyano-[1,3]dioxolan-2-ylidene-acetic acid ethyl ester (prepared as described by Neidlein and Kikelj, Synthesis, 1988, 981, 266 mg, 1.45 mmol, 1.0 eq), N-cyclopropyl-3-hydrazino-4-methyl-benzamide trifluoroacetate (Example 6 C, 463 mg, 1.45 mmol, 1.0 eq), and triethylamine (405 μL, 2.9 mmol, 2.0 eq) in 20 mL of ethanol was heated to 65° C. overnight. After cooling to room temperature, the mixture was concentrated and the residue purified by flash chromatography on silica gel (eluted with 1/1 hexanes/EtOAc followed by 100% EtOAc) to provide the desired compound as a tan solid (350 mg, 62%). HPLC (4 minute 10-95 gradient) tR 1.59 min; MS ink 389.06 [M+H]+; 1H NMR (CD3OD), δ 7.87 (d, J=7.9 Hz, 1 H), 7.78 (s, 1 H), 7.49 (d, J=7.8 Hz, 1 H), 4.29 (dd, J=14.9, 6.9 Hz, 2 H), 4.19 (d, J=4.3 Hz, 2 H), 3.84 (d, J=4.4 Hz, 2 H), 2.84 (m, 1 H), 2.22 (s, 3 H), 1.35 (t, J=7.3 Hz, 3 H), 0.81 (d, J=5.3 Hz, 2 H), 0.63 (s, 2 H) ppm. the mixture was concentrated the residue purified by flash chromatography on silica gel (eluted with 1/1 hexanes/EtOAc followed by 100% EtOAc)

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

Procedure: A stirred solution of cyano-[1,3]dioxolan-2-ylidene-acetic acid ethyl ester (prepared as described by Neidlein and Kikelj, Synthesis, 1988, 981, 266 mg, 1.45 mmol, 1.0 eq), N-cyclopropyl-3-hydrazino-4-methyl-benzamide trifluoroacetate (Example 6C, 463 mg, 1.45 mmol, 1.0 eq), and triethylamine (405 μL, 2.9 mmol, 2.0 eq) in 20 mL of ethanol was heated to 65° C. overnight. After cooling to room temperature, the mixture was concentrated and the residue purified by flash chromatography on silica gel (eluted with 1/1 hexanes/EtOAc followed by 100% EtOAc) to provide the desired compound as a tan solid (350 mg, 62%). HPLC (4 minute 10-95 gradient) tR 1.59 min; MS m/z 389.06 [M+H]+; 1H NMR (CD3OD), δ 7.87 (d, J=7.9 Hz, 1 H), 7.78 (s, 1 H), 7.49 (d, J=7.8 Hz, 1 H), 4.29 (dd, J=14.9, 6.9 Hz, 2 H), 4.19 (d, J=4.3 Hz, 2 H), 3.84 (d, J=4.4 Hz, 2 H), 2.84 (m, 1 H), 2.22 (s, 3 H), 1.35 (t, J=7.3 Hz, 3 H), 0.81 (d, J=5.3 Hz, 2 H), 0.63 (s, 2 H) ppm. the mixture was concentrated the residue purified by flash chromatography on silica gel (eluted with 1/1 hexanes/EtOAc followed by 100% EtOAc)

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

Procedure: A stirred solution of cyano-[1,3]dioxolan-2-ylidene-acetic acid ethyl ester (prepared as described by Neidlein and Kikelj, Synthesis, 1988, 981, 266 mg, 1.45 mmol, 1.0 eq), N-cyclopropyl-3-hydrazino-4-methyl-benzamide trifluoroacetate (Example 6C, 463 mg, 1.45 mmol, 1.0 eq), and triethylamine (405 μL, 2.9 mmol, 2.0 eq) in 20 mL of ethanol was heated to 65° C. overnight. After cooling to room temperature, the mixture was concentrated and the residue purified by flash chromatography on silica gel (eluted with 1/1 hexanes/EtOAc followed by 100% EtOAc) to provide the desired compound as a tan solid (350 mg, 62%). HPLC (4 minute 10-95 gradient) tR 1.59 min; MS ink 389.06 [M+H]+; 1H NMR (CD3OD), δ 7.87 (d, J=7.9 Hz, 1H), 7.78 (s, 1H), 7.49 (d, J=7.8 Hz, 1H), 4.29 (dd, J=14.9, 6.9 Hz, 2H), 4.19 (d, J=4.3 Hz, 2H), 3.84 (d, J=4.4 Hz, 2H), 2.84 (m, 1H), 2.22 (s, 3H), 1.35 (t, J=7.3 Hz, 3H), 0.81 (d, J=5.3 Hz, 2H), 0.63 (s, 2H) ppm. the mixture was concentrated the residue purified by flash chromatography on silica gel (eluted with 1/1 hexanes/EtOAc followed by 100% EtOAc)

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

Procedure: A stirred solution of cyano-[1,3]dioxolan-2-ylidene-acetic acid ethyl ester (prepared as described by Neidlein and Kikelj, Synthesis, 1988, 981, 266 mg, 1.45 mmol, 1.0 eq), N-cyclopropyl-3-hydrazino-4-methyl-benzamide trifluoroacetate (Example 6C, 463 mg, 1.45 mmol, 1.0 eq), and triethylamine (405 μL, 2.9 mmol, 2.0 eq) in 20 mL of ethanol was heated to 65° C. overnight. After cooling to room temperature, the mixture was concentrated and the residue purified by flash chromatography on silica gel (eluted with 1/1 hexanes/EtOAc followed by 100% EtOAc) to provide the desired compound as a tan solid (350 mg, 62%). HPLC (4 minute 10-95 gradient) tR1.59 min; MS ink 389.06 [M+H]+; 1H NMR (CD3OD), δ 7.87 (d, J=7.9 Hz, 1H), 7.78 (s, 1H), 7.49 (d, J=7.8 Hz, 1H), 4.29 (dd, J=14.9, 6.9 Hz, 2H), 4.19 (d, J=4.3 Hz, 2H), 3.84 (d, J=4.4 Hz, 2H), 2.84 (m, 1H), 2.22 (s, 3H), 1.35 (t, J=7.3 Hz, 3H), 0.81 (d, J=5.3 Hz, 2H), 0.63 (s, 2H) ppm. the mixture was concentrated the residue purified by flash chromatography on silica gel (eluted with 1/1 hexanes/EtOAc followed by 100% EtOAc)

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

Procedure: A stirred solution of cyano-[1,3]dioxolan-2-ylidene-acetic acid ethyl ester (prepared as described by Neidlein and Kikelj, Synthesis, 1988, 981, 266 mg, 1.45 mmol, 1.0 eq), N-cyclopropyl-3-hydrazino-4-methyl-benzamide trifluoroacetate (Example 6 C, 463 mg, 1.45 mmol, 1.0 eq), and triethylamine (405 μL, 2.9 mmol, 2.0 eq) in 20 mL of ethanol was heated to 65° C. overnight. After cooling to room temperature, the mixture was concentrated and the residue purified by flash chromatography on silica gel (eluted with 1/1 hexanes/EtOAc followed by 100% EtOAc) to provide the desired compound as a tan solid (350 mg, 62%). HPLC (4 minute 10-95 gradient) tR 1.59 min; MS ink 389.06 [M+H]+; 1H NMR (CD3OD), δ 7.87 (d, J=7.9 Hz, 1 H), 7.78 (s, 1 H), 7.49 (d, J=7.8 Hz, 1 H), 4.29 (dd, J=14.9, 6.9 Hz, 2 H), 4.19 (d, J=4.3 Hz, 2 H), 3.84 (d, J=4.4 Hz, 2 H), 2.84 (m, 1 H), 2.22 (s, 3 H), 1.35 (t, J=7.3 Hz, 3 H), 0.81 (d, J=5.3 Hz, 2 H), 0.63 (s, 2 H) ppm. the mixture was concentrated the residue purified by flash chromatography on silica gel (eluted with 1/1 hexanes/EtOAc followed by 100% EtOAc)

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

Procedure: A stirred solution of cyano-[1,3]dioxolan-2-ylidene-acetic acid ethyl ester (prepared as described by Neidlein and Kikelj, Synthesis, 1988, 981, 266 mg, 1.45 mmol, 1.0 eq), N-cyclopropyl-3-hydrazino-4-methyl-benzamide trifluoroacetate (Example 6C, 463 mg, 1.45 mmol, 1.0 eq), and triethylamine (405 μL, 2.9 mmol, 2.0 eq) in 20 mL of ethanol was heated to 65° C. overnight. After cooling to room temperature, the mixture was concentrated and the residue purified by flash chromatography on silica gel (eluted with 1/1 hexanes/EtOAc followed by 100% EtOAc) to provide the desired compound as a tan solid (350 mg, 62%). HPLC (4 minute 10-95 gradient) tR 1.59 min; MS m/z 389.06 [M+H]+; 1H NMR (CD3OD), δ 7.87 (d, J=7.9 Hz, 1 H), 7.78 (s, 1 H), 7.49 (d, J=7.8 Hz, 1 H), 4.29 (dd, J=14.9, 6.9 Hz, 2 H), 4.19 (d, J=4.3 Hz, 2 H), 3.84 (d, J=4.4 Hz, 2 H), 2.84 (m, 1 H), 2.22 (s, 3 H), 1.35 (t, J=7.3 Hz, 3 H), 0.81 (d, J=5.3 Hz, 2 H), 0.63 (s, 2 H) ppm. the mixture was concentrated the residue purified by flash chromatography on silica gel (eluted with 1/1 hexanes/EtOAc followed by 100% EtOAc)