1-aminoimidazolidin-2-one

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

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

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

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

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

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

Procedure: To a solution of 6,7-dimethoxy-3-isoquinolinecarboxylic acid (6.99 g, 30.0 mmol) in 300 ml of N,N-dimethylformamide were added triethylamine (12.14 g, 120.0 mmol) and diphenyl chlorophosphate (80.6 g, 30.0 mmol) at 0° C. After stirring for 4 hours at 0° C., N-amino-2-oxoimidazolidine (3.03 g, 30.0 mmol) was added, and the mixture was stirred at 0° C. overnight. Ammonium salts (2.0 g) were filtered off, and the filtrate was evaporated in vacuo. The residue was triturated with a 1:1 mixture of water and ethyl acetate. The solid was filtered off and triturated twice with water at pH 8 for 3 hours. The remaining solid was filtered off, washed with water and dried in vacuo. Yield: 4.30 g; melting point 220° C. (dec.). the mixture was stirred at 0° C. overnight Ammonium salts (2.0 g) were filtered off the filtrate was evaporated in vacuo The residue was triturated with a 1:1 mixture of water and ethyl acetate The solid was filtered off triturated twice with water at pH 8 for 3 hours The remaining solid was filtered off washed with water dried in vacuo

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

Procedure: To a suspension of 1,4-dihydro-6,7-dimethoxy-4-oxo-3-quinolinecarboxylic acid (39.9 g, 0.160 mol) in 3.2 l of N,N-dimethylformamide, triethylamine (32.4 g, 0.320 mol) was added. At 0° C. and under nitrogen protection, diphenyl chlorophosphate (43.0 g, 0.160 mol) was added dropwise and the mixture was stirred for 6 hours at 0° C. A solution of N-amino-imidazolidine-2-one (16.2 g, 0.160 mol) in N,N-dimethylformamide was added and stirring was continued at 0° C. overnight. The triethyl ammonium salt (26 g) was filtered off and the filtrate evaporated in vacuo. The residual oil was triturated with 1 l of ethyl acetate and 1 l of water. The resulting solid was filtered off, washed with water and ethyl acetate and dried in vacuo. The crude product was stirred with 270 ml of 0.2N sodium hydroxide solution of 2 days, filtered off, washed with water and dried in vacuo to give 23.2 g of the title compound, melting point>300° C. was added stirring was continued at 0° C. overnight The triethyl ammonium salt (26 g) was filtered off the filtrate evaporated in vacuo The residual oil was triturated with 1 l of ethyl acetate and 1 l of water The resulting solid was filtered off washed with water and ethyl acetate dried in vacuo The crude product was stirred with 270 ml of 0.2N sodium hydroxide solution of 2 days filtered off washed with water dried in vacuo

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

Procedure: To a suspension of 1,4-dihydro-6,7-dimethoxy-4-oxo-3-quinolinecarboxylic acid (39.9 g, 0.160 mol) in 3.2 l of N,N-dimethylformamide, triethylamine (32.4 g, 0.320 mol) was added. At 0° C. and under nitrogen protection, diphenyl chlorophosphate (43.0 g, 0.160 mol) was added dropwise and the mixture was stirred for 6 hours at 0° C. A solution of N-amino-imidazolidine-2-one (16.2 g, 0.160 mol) in N,N-dimethylformamide was added and stirring was continued at 0° C. overnight. The triethyl ammonium salt (26 g) was filtered off and the filtrate evaporated in vacuo. The residual oil was triturated with 1 l of ethyl acetate and 1 l of water. The resulting solid was filtered off, washed with water and ethyl acetate and dried in vacuo. The crude product was stirred with 270 ml of 0.2N sodium hydroxide solution of 2 days, filtered off, washed with water and dried in vacuo to give 23.2 g of the title compound, melting point>300° C. was added stirring was continued at 0° C. overnight The triethyl ammonium salt (26 g) was filtered off the filtrate evaporated in vacuo The residual oil was triturated with 1 l of ethyl acetate and 1 l of water The resulting solid was filtered off washed with water and ethyl acetate dried in vacuo The crude product was stirred with 270 ml of 0.2N sodium hydroxide solution of 2 days filtered off washed with water dried in vacuo

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

Procedure: 3.2 ml. of (phenylthio)carbonyl chloride are dissolved in 30 ml. of dioxane and a solution of 2.63 g. of 1-amino-2-imidazolidinone in a mixture of 10 ml. of dioxane and 10 ml. of water is added. 2N sodium hydroxide solution is added dropwise at room temperature so that the pH is about 7.5-8.0. About 15 ml. of 2N sodium hydroxide are required. The dioxane is then distilled off. An oil separates which crystallizes after a short while to give 3.2 g. of (2-oxo-1-imidazolidinyl)carbamothioic acid, S-phenyl ester, m.p. 154°-159° (after recrystallization from ethyl acetate). The dioxane is then distilled off An oil separates which crystallizes after a short while to give 3.2 g of (2-oxo-1-imidazolidinyl)carbamothioic acid, S-phenyl ester, m.p. 154°-159° (after recrystallization from ethyl acetate)

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

Procedure: 1.01 g. (0.01 mol.) of 1-amino-2-imidazolidinone are dissolved in 20 ml. of anhydrous tetrahydrofuran and 20 ml. of a 1M solution of phosgene in toluene are added at 0°. The solution is stirred overnight at room temperature. The almost clear solution is filtered and evaporated to dryness. The 1-(chlorocarbonylamino)-2-oxoimidazolidine is obtained as an oily residue which is used without further purification. The almost clear solution is filtered evaporated to dryness

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

Procedure: 1.01 g. (0.01 mol.) of 1-amino-2-imidazolidinone are dissolved in 20 ml. of anhydrous tetrahydrofuran and 20 ml. of a 1M solution of phosgene in toluene are added at 0°. The solution is stirred overnight at room temperature. The almost clear solution is filtered and evaporated to dryness. The 1-(chlorocarbonylamino)-2-oxoimidazolidine is obtained as an oily residue which is used without further purification. The almost clear solution is filtered evaporated to dryness

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

Procedure: The title compound (18.0 mg, 66%) was synthesized from 1-[3-(7-fluoro-quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyrazin-5-yl]-ethanone (20.0 mg, 0.06 mmol) and 1-amino-imidazolidin-2-one (28.2 mg, 0.19 mmol) using the same procedure as described in the synthesis of example 72. 1H-NMR (400 MHz, DMSO-d6) δ ppm 9.42 (s, 1H), 8.93 (dd, 1H), 8.41 (d, 1H), 8.20 (d, 1H), 7.83 (d, 1H), 7.54 (dd, 1H), 7.38 (s, 1H), 6.25 (s, 2H), 3.86 (t, 2H), 3.42 (t, 2H), 2.38 (s, 3H). LCMS (method A): [MH]+=401, tR=2.01 min. as described in the synthesis of example 72