2-Chlorobenzoylacetonitrile

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

Procedure: A solution of 2-chlorobenzoylacetonitrile (15.9 g, 89 mmol) and hydrazine hydrate (8.9 g, 0.18 mol) in ethanol (2 ml) was heated at reflux for 22 hr. After cooling to room temperature, the reaction was concentrated, in vacuo. The residue was dissolved in ethyl acetate, washed with water and brine, dried (MgSO4), and concentrated, in vacuo, to a brown oil. Flash chromatography using 10% ethyl acetate in methylene chloride, changing to 5% methanol in methylene chloride as eluant afforded title product I-1A-1a (17.3 g, quantitative): +ESI MS (M+1) 194.2; 1H NMR (400 MHz, CD3OD) δ 7.60–7.25 (m, 4H), 5.99 (br s, 1H). at reflux for 22 hr the reaction was concentrated, in vacuo The residue was dissolved in ethyl acetate washed with water and brine dried (MgSO4) concentrated, in vacuo, to a brown oil

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

Procedure: A solution of 2-chlorobenzoylacetonitrile (1.0 g, 5.6 mmol, 1.0 eq) and diphenylformamidine (1.10 g, 5.6 mmol, 1.0 eq) in 50 mL of toluene was heated to 85° C. overnight. The heat source was removed and desired product slowly began to precipitate from solution. The resulting solid was filtered and dried to provide the desired product (826 mg, 52%). HPLC (4 minute 10-90 gradient) tR 3.13 min; MS m/z 283.2 [M+H]+. The heat source was removed to precipitate from solution The resulting solid was filtered dried

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

Procedure: A solution of 2-chlorobenzoylacetonitrile (1.0 g, 5.6 mmol, 1.0 eq) and diphenylformamidine (1.10 g, 5.6 mmol, 1.0 eq) in 50 mL of toluene was heated to 85° C. overnight. The heat source was removed and desired product slowly began to precipitate from solution. The resulting solid was filtered and dried to provide the desired product (826 mg, 52%). HPLC (4 minute 10-90 gradient) tR 3.13 min; MS m/z 283.2 [M+H]+. The heat source was removed to precipitate from solution The resulting solid was filtered dried

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

Procedure: A solution of 2-chlorobenzoylacetonitrile (1.0 g, 5.6 mmol, 1.0 eq) and diphenylformamidine (1.10 g, 5.6 mmol, 1.0 eq) in 50 mL of toluene was heated to 85° C. overnight. The heat source was removed and desired product slowly began to precipitate from solution. The resulting solid was filtered and dried to provide the desired product (826 mg, 52%). HPLC (4 minute 10-90 gradient) tR 3.13 min; MS m/z 283.2 [M+H]+. The heat source was removed to precipitate from solution The resulting solid was filtered dried

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

Procedure: A solution of 2-chlorobenzoylacetonitrile (1.0 g, 5.6 mmol, 1.0 eq) and diphenylformamidine (1.10 g, 5.6 mmol, 1.0 eq) in 50 mL of toluene was heated to 85° C. overnight. The heat source was removed and desired product slowly began to precipitate from solution. The resulting solid was filtered and dried to provide the desired product (826 mg, 52%). HPLC (4 minute 10-90 gradient) tR 3.13 min; MS m/z 283.2 [M+H]+. The heat source was removed to precipitate from solution The resulting solid was filtered dried

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

Procedure: A solution of 2-chlorobenzoylacetonitrile (15.9 g, 89 mmol) and hydrazine hydrate (8.9 g, 0.18 mol) in ethanol (2 ml) was heated at reflux for 22 hr. After cooling to room temperature, the reaction was concentrated, in vacuo. The residue was dissolved in ethyl acetate, washed with water and brine, dried (MgSO4), and concentrated, in vacuo, to a brown oil. Flash chromatography using 10% ethyl acetate in methylene chloride, changing to 5% methanol in methylene chloride as eluant afforded title product I-1A-1a (17.3 g, quantitative): +ESI MS (M+1) 194.2; 1H NMR (400 MHz, CD3OD) δ 7.60–7.25 (m, 4H), 5.99 (br s, 1H). at reflux for 22 hr the reaction was concentrated, in vacuo The residue was dissolved in ethyl acetate washed with water and brine dried (MgSO4) concentrated, in vacuo, to a brown oil

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

Procedure: A solution of 2-chlorobenzoylacetonitrile (15.9 g, 89 mmol) and hydrazine hydrate (8.9 g, 0.18 mol) in ethanol (2 ml) was heated at reflux for 22 hr. After cooling to room temperature, the reaction was concentrated, in vacuo. The residue was dissolved in ethyl acetate, washed with water and brine, dried (MgSO4), and concentrated, in vacuo, to a brown oil. Flash chromatography using 10% ethyl acetate in methylene chloride, changing to 5% methanol in methylene chloride as eluant afforded title product I-1A-1a (17.3 g, quantitative): +ESI MS (M+1) 194.2; 1H NMR (400 MHz, CD3OD) δ 7.60–7.25 (m, 4H), 5.99 (br s, 1H). at reflux for 22 hr the reaction was concentrated, in vacuo The residue was dissolved in ethyl acetate washed with water and brine dried (MgSO4) concentrated, in vacuo, to a brown oil

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

Procedure: A solution of 2-chlorobenzoylacetonitrile (1.0 g, 5.6 mmol, 1.0 eq) and diphenylformamidine (1.10 g, 5.6 mmol, 1.0 eq) in 50 mL of toluene was heated to 85° C. overnight. The heat source was removed and desired product slowly began to precipitate from solution. The resulting solid was filtered and dried to provide the desired product (826 mg, 52%). HPLC (4 minute 10-90 gradient) tR 3.13 min; MS m/z 283.2 [M+H]+. The heat source was removed to precipitate from solution The resulting solid was filtered dried

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

Procedure: A solution of 2-chlorobenzoylacetonitrile (15.9 g, 89 mmol) and hydrazine hydrate (8.9 g, 0.18 mol) in ethanol (2 ml) was heated at reflux for 22 hr. After cooling to room temperature, the reaction was concentrated, in vacuo. The residue was dissolved in ethyl acetate, washed with water and brine, dried (MgSO4), and concentrated, in vacuo, to a brown oil. Flash chromatography using 10% ethyl acetate in methylene chloride, changing to 5% methanol in methylene chloride as eluant afforded title product I-3A-9a (17.3 g, quantitative): +ESI MS (M+1) 194.2; 1H NMR (400 MHz, CD3OD) δ 7.60-7.25 (m, 4H), 5.99 (br s, 1H). at reflux for 22 hr the reaction was concentrated, in vacuo The residue was dissolved in ethyl acetate washed with water and brine dried (MgSO4) concentrated, in vacuo, to a brown oil

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-chlorobenzoylacetonitrile (400 g, 2.23 mol) in ethanol (9 L) was added hydrazine hydrate (221 g, 4.42 mol) over 15 minutes while maintaining internal reaction temperature at 15 to 25° C. The mixture was then heated at 75° C. for 20 hr. After cooling, the reaction was concentrated, in vacuo, to give a brown oil. The residue was dissolved in ethyl acetate (4 L), washed with half saturated brine (4 L), and then dried (Na2SO4) to a give a crude, dark orange solution of 5-(2-chlorophenyl)-2H-pyrazol-3-ylamine that was carried directly into the next reaciton: +ESI MS (M+1) 194.0. The mixture was then heated at 75° C. for 20 hr After cooling the reaction was concentrated, in vacuo to give a brown oil washed with half saturated brine (4 L) dried (Na2SO4) to

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

Procedure: A solution of 2-chlorobenzoylacetonitrile (1.0 g, 5.6 mmol, 1.0 eq) and diphenylformamidine (1.10 g, 5.6 mmol, 1.0 eq) in 50 mL of toluene was heated to 85° C. overnight. The heat source was removed and desired product slowly began to precipitate from solution. The resulting solid was filtered and dried to provide the desired product (826 mg, 52%). HPLC (4 minute 10-90 gradient) tR 3.13 min; MS m/z 283.2 [M+H]+. The heat source was removed to precipitate from solution The resulting solid was filtered dried

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

Procedure: A solution of 2-chlorobenzoylacetonitrile (1.0 g, 5.6 mmol, 1.0 eq) and diphenylformamidine (1.10 g, 5.6 mmol, 1.0 eq) in 50 mL of toluene was heated to 85° C. overnight. The heat source was removed and desired product slowly began to precipitate from solution. The resulting solid was filtered and dried to provide the desired product (826 mg, 52%). HPLC (4 minute 10-90 gradient) tR 3.13 min; MS m/z 283.2 [M+H]+. The heat source was removed to precipitate from solution The resulting solid was filtered dried