2-(diethylamino)acetohydrazide

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

Procedure: In the manner given in Preparation 1, a solution of 1,3-dihydro-7-chloro-5-phenyl-2H-1,4-benzodiazepine-2-thione and (diethylamino)acetic acid hydrazide in n-butyl alcohol is reacted to give 8-chloro-1-[(diethyl amino)methyl]-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepine, which is recrystallized from ethyl acetateSkellysolve B hexanes and has a melting point of 131.5°-132.5° C. Anal. calcd. for C21H22ClN5 : C, 66.39; H, 5.84; Cl, 9.33; N, 18.44. Found: C, 66.20; H, 6.06; Cl, 9.29; N, 18.55. Preparation 8 8-Nitro-1-[(diethylamino)methyl]-6-phenyl4H-s-triazolo[4,3-a][1,4]benzodiazepine In the manner given in Preparation 1

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of ethoxy[3-(4-fluorophenyl)(1H-indazol-5-yl)]methanimine hydrochloride (0.400 g, 1.25 mmol) in 4 mL of anhydrous ethanol was prepared and cooled to 0° C. An excess of a commercial solution of sodium methoxide in methanol (0.858 mL, 4.37 M)) was added followed by 3 equivalents of N-amino-2-(diethylamino)acetamide (0.545 g, 3.75 mmol) as a solid. The reaction mixture was heated to reflux temperature in a sealed tube for 2 days. The reaction was then quenched with water, the pH adjusted to neutral and the crude product extracted with ethyl acetate. The residue was purified by preparative HPLC (0.052 g, 11% yield): 1H NMR (CD3OD) δ 8.70 (s, 1H), 8.11-8.02 (m, 3H), 7.67 (d, 1H), 7.29 (td, 2H), 3.8 (s, 1H), 2.68 (q, 4H), 1.15 (t, 3H); ES-MS (m/z) 365 [M+H]+. was prepared The reaction mixture was heated to reflux temperature in a sealed tube for 2 days The reaction was then quenched with water extracted with ethyl acetate The residue was purified by preparative HPLC (0.052 g, 11% yield)

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

Procedure: To a solution of methyl 2-(diethylamino)acetate (4.167 mL, 27.55 mmol) in 4 mL of anhydrous ethanol was added anhydrous hydrazine (1.336 mL, 27.55 mmol). The solution was heated to reflux temperature overnight. The solvent was then removed under reduced pressure and the product was isolated as an oil in a quantitative yield and was used without further purification: 1H NMR (CDCl3) δ 8.3 (br s, 1H), 3.83 (br s, 2H), 3.08 (s, 2H), 2.51 (q, 4H), 1.00 (t, 6H); ES-MS (m/z) 146 [M+H]+. The solution was heated to reflux temperature overnight The solvent was then removed under reduced pressure the product was isolated as an oil in a quantitative yield was used without further purification

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

Procedure: A solution of 1,3-dihydro-7-chloro-5-phenyl-2H-1,4-benzodiazepine-2-thione and (diethylamino)acetic acid hydrazide in n-butyl alcohol was refluxed to give 8-chloro-1-[(diethylamino)methyl]-6-phenyl-4H-s-triazolo[4,3-a]-[1,4]benzodiazepine, which was recrystallized from ethyl acetate-Skellysolve B hexanes and was identical to the compound obtained in Example 4.

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of ethoxy[3-(4-fluorophenyl)(1H-indazol-5-yl)]methanimine hydrochloride (0.400 g, 1.25 mmol) in 4 mL of anhydrous ethanol was prepared and cooled to 0° C. An excess of a commercial solution of sodium methoxide in methanol (0.858 mL, 4.37 M)) was added followed by 3 equivalents of N-amino-2-(diethylamino)acetamide (0.545 g, 3.75 mmol) as a solid. The reaction mixture was heated to reflux temperature in a sealed tube for 2 days. The reaction was then quenched with water, the pH adjusted to neutral and the crude product extracted with ethyl acetate. The residue was purified by preparative HPLC (0.052 g, 11% yield): 1H NMR (CD3OD) δ 8.70 (s, 1H), 8.11–8.02 (m, 3H), 7.67 (d, 1H), 7.29 (td, 2H), 3.8 (s, 1H), 2.68 (q, 4H), 1.15 (t, 3H); ES-MS (m/z) 365 [M+H]+. was prepared The reaction mixture was heated to reflux temperature in a sealed tube for 2 days The reaction was then quenched with water extracted with ethyl acetate The residue was purified by preparative HPLC (0.052 g, 11% yield)

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

Procedure: To a solution of methyl 2-(diethylamino)acetate (4.167 mL, 27.55 mmol) in 4 mL of anhydrous ethanol was added anhydrous hydrazine (1.336 mL, 27.55 mmol). The solution was heated to reflux temperature overnight. The solvent was then removed under reduced pressure and the product was isolated as an oil in a quantitative yield and was used without further purification: 1H NMR (CDCl3) δ 8.3 (br s, 1H), 3.83 (br s, 2H), 3.08 (s, 2H), 2.51 (q, 4H), 1.00 (t, 6H); ES-MS (m/z) 146 [M+H]+. The solution was heated to reflux temperature overnight The solvent was then removed under reduced pressure the product was isolated as an oil in a quantitative yield was used without further purification

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

Procedure: To a solution of methyl 2-(diethylamino)acetate (4.167 mL, 27.55 mmol) in 4 mL of anhydrous ethanol was added anhydrous hydrazine (1.336 mL, 27.55 mmol). The solution was heated to reflux temperature overnight. The solvent was then removed under reduced pressure and the product was isolated as an oil in a quantitative yield and was used without further purification: 1H NMR (CDCl3) δ 8.3 (br s, 1H), 3.83 (br s, 2H), 3.08 (s, 2H), 2.51 (q, 4H), 1.00 (t, 6H); ES-MS (m/z) 146 [M+H]+. The solution was heated to reflux temperature overnight The solvent was then removed under reduced pressure the product was isolated as an oil in a quantitative yield was used without further purification

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of ethoxy[3-(4-fluorophenyl)(1H-indazol-5-yl)]methanimine hydrochloride (0.400 g, 1.25 mmol) in 4 mL of anhydrous ethanol was prepared and cooled to 0° C. An excess of a commercial solution of sodium methoxide in methanol (0.858 mL, 4.37 M)) was added followed by 3 equivalents of N-amino-2-(diethylamino)acetamide (0.545 g, 3.75 mmol) as a solid. The reaction mixture was heated to reflux temperature in a sealed tube for 2 days. The reaction was then quenched with water, the pH adjusted to neutral and the crude product extracted with ethyl acetate. The residue was purified by preparative HPLC (0.052 g, 11% yield): 1H NMR (CD3OD) δ 8.70 (s, 1H), 8.11–8.02 (m, 3H), 7.67 (d, 1H), 7.29 (td, 2H), 3.8 (s, 1H), 2.68 (q, 4H), 1.15 (t, 3H); ES-MS (m/z) 365 [M+H]+. was prepared The reaction mixture was heated to reflux temperature in a sealed tube for 2 days The reaction was then quenched with water extracted with ethyl acetate The residue was purified by preparative HPLC (0.052 g, 11% yield)

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

Procedure: To a solution of methyl 2-(diethylamino)acetate (4.167 mL, 27.55 mmol) in 4 mL of anhydrous ethanol was added anhydrous hydrazine (1.336 mL, 27.55 mmol). The solution was heated to reflux temperature overnight. The solvent was then removed under reduced pressure and the product was isolated as an oil in a quantitative yield and was used without further purification: 1H NMR (CDCl3) δ 8.3 (br s, 1H), 3.83 (br s, 2H), 3.08 (s, 2H), 2.51 (q, 4H), 1.00 (t, 6H); ES-MS (m/z) 146 [M+H]+. The solution was heated to reflux temperature overnight The solvent was then removed under reduced pressure the product was isolated as an oil in a quantitative yield was used without further purification

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

Procedure: In the manner given in Preparation 1, a solution of 1,3-dihydro-7-chloro-5-phenyl-2H-1,4-benzodiazepine-2-thione and (diethylamino)acetic acid hydrazide in n-butyl alcohol is reacted to give 8-chloro-1-[(diethyl amino)methyl]-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepine, which is recrystallized from ethyl acetateSkellysolve B hexanes and has a melting point of 131.5°-132.5° C. Anal. calcd. for C21H22ClN5 : C, 66.39; H, 5.84; Cl, 9.33; N, 18.44. Found: C, 66.20; H, 6.06; Cl, 9.29; N, 18.55. Preparation 8 8-Nitro-1-[(diethylamino)methyl]-6-phenyl4H-s-triazolo[4,3-a][1,4]benzodiazepine In the manner given in Preparation 1