1-(2-aminoethyl)imidazolidin-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:; See reaction.notes.procedure_details.

Procedure: To a mixture of 6.5 g of commercially available 1-(2-aminoethyl)-2-imidazolidone and 50 ml benzene was added 5.5 ml of phenyl isocyanate. The strongly exothermic reaction was moderated by cooling to 25°. The mixture was stirred at 25° for 4 hr. It was cooled in ice and the mixture was filtered. The solid product was crystallized from 250 ml of acetone to give 6.8 g of white 1-[2-(2-oxo-1-imidazolidinyl)ethyl]-3-phenylurea, mp 162°-164°. The strongly exothermic reaction by cooling to 25° It was cooled in ice the mixture was filtered The solid product was crystallized from 250 ml of acetone

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

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

Procedure: Combine {4-[2-(2-chloro-5-fluoro-pyrimidin-4-yl)-benzo[b]thiophen-7-yl]-6-fluoro-pyridin-3-ylmethyl}-dimethyl-amine (0.25 g, 0.59 mmol) and triethylamine (0.25 mL, 1.78 mmol) in n-butanol (8.0 mL). Add 1-(2-aminoethyl) imidazolidin-2-one (0.23 g, 1.78 mmol). Heat the reaction mixture at 120° C. overnight (15 hours), then cool to room temperature. Dilute the reaction mixture with ethyl acetate, and wash with water and saturated aqueous sodium chloride. Separate the organic layer from aqueous layer and dry over MgSO4. After filtration, remove the organic solvent to give a crude. Purify the crude by column chromatography (0.5% to 10% 2 N NH3 in methanol solution/dichloromethane) to afford the title compound (0.19 g, 63%). MS (ES) m/z 510 [M+1]+. cool to room temperature wash with water and saturated aqueous sodium chloride Separate the organic layer from aqueous layer dry over MgSO4 After filtration remove the organic solvent to give a crude Purify the crude by column chromatography (0.5% to 10% 2 N NH3 in methanol solution/dichloromethane)

Conditions: temp:170.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 5-Bromo-2-chloro-4-(5-(piperidin-1-ylmethyl)thiophen-2-yl)pyrimidine (0.3 g, 0.8 mmol), 1-(2-aminoethyl)imidazolidin-2-one (0.123 g, 0.96 mmol) and isopropyl alcohol were all placed in a microwave tube. The tube was capped and heated to 170° C. in a Personal Chemistry microwave for 10 min. The reaction then diluted with dichloromethane washed with water, saturated sodium bicarbonate, water and brine. The organic layer was dried with sodium sulfate and purified by flash chromatography using a gradient of 2 to 12% methanol in dichloromethane to give a light yellow solid (0.23 g). MS (M+H)+ 465/476. all placed in a microwave tube The tube was capped The reaction washed with water, saturated sodium bicarbonate, water and brine The organic layer was dried with sodium sulfate purified by flash chromatography

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 5-Bromo-2-chloro-4-(5-chlorothiophen-2-yl)pyrimidine (0.4g, 1.3 mmol), N-methyl pyrrolidone (3 mL), potassium carbonate (0.358 g, 2.6 mmol) and 1-(2-aminoethyl)-imidazolidin-2-one (0.2 g, 1.54 mmol) were all placed in a microwave tube. The reaction was heated to 150° C. for 20 min in a Personal Chemistry microwave. A saturated solution of sodium bicarbonate was added to the reaction mixtue, which was extracted three times with dichloromethane. The organic layer was dried with sodium sulfate and purified by flash chromatography on silica gel using gradient of 0 to 10% methanol in dichloromethane to obtain a white solid. Yield=0.41 g. MS (M+H)+ 402/404. all placed in a microwave tube was extracted three times with dichloromethane The organic layer was dried with sodium sulfate purified by flash chromatography on silica gel using gradient of 0 to 10% methanol in dichloromethane to obtain a white solid

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 5-Bromo-2-chloro-4-(thiophen-2-yl)pyrimidine (2.0 g, 7.25 mmol) dissolved in N-methyl pyrrolidone (25 mL) was treated with potassium carbonate (2 g, 14.5 mmol) and 1-(2-aminoethyl)imidazolidin-2-one (1.125 g, 8.71 mmol). The reaction was heated to 110° C. overnight. The reaction was poured into ice water and extracted with dichloromethane. The organic layer was washed with saturated aqueous sodium bicarbonate, water and brine and then dried with sodium sulfate. Purification was achieved by flash chromatography using a gradient of 0 to 10% methanol in dichloromethane to obtain a yellow solid. Yield=2 g. MS (M+H)+ 368/370. extracted with dichloromethane The organic layer was washed with saturated aqueous sodium bicarbonate, water and brine dried with sodium sulfate Purification to obtain a yellow solid

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 5-Bromo-2-chloro-4-(thiophen-2-yl)pyrimidine (2.0 g, 7.25 mmol) dissolved in N-methyl pyrrolidone (25 mL) was treated with potassium carbonate (2 g, 14.5 mmol) and 1-(2-aminoethyl)imidazolidin-2-one (1.125 g, 8.71 mmol). The reaction was heated to 110° C. overnight. The reaction was poured into ice water and extracted with dichloromethane. The organic layer was washed with saturated aqueous sodium bicarbonate, water and brine and then dried with sodium sulfate. Purification was achieved by flash chromatography using a gradient of 0 to 10% methanol in dichloromethane to obtain a yellow solid. Yield=2 g. MS (M+H)+ 368/370. extracted with dichloromethane The organic layer was washed with saturated aqueous sodium bicarbonate, water and brine dried with sodium sulfate Purification to obtain a yellow solid

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

Procedure: 4-(5-Bromothiophen-2-yl)-5-methyl-2-(methylsulfonyl)pyrimidine (2 g, 6 mmol) in toluene (10 mL) was treated with 1-(2-aminoethyl)imidazolidin-2-one (1.489 g, 10.2 mmol) and the reaction stirred at 120° C. overnight. The volatiles were removed in vacuo and the residue purified by flash chromatography using a gradient of 2 to 10% methanol in dichloromethane to obtain a light yellow solid (1.8 g). MS (M+H)+ 383. The volatiles were removed in vacuo the residue purified by flash chromatography

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

Procedure: 4-(5-Bromothiophen-2-yl)-5-methyl-2-(methylsulfonyl)pyrimidine (2 g, 6 mmol) in toluene (10 mL) was treated with 1-(2-aminoethyl)imidazolidin-2-one (1.489 g, 10.2 mmol) and the reaction stirred at 120° C. overnight. The volatiles were removed in vacuo and the residue purified by flash chromatography using a gradient of 2 to 10% methanol in dichloromethane to obtain a light yellow solid (1.8 g). MS (M+H)+ 383. The volatiles were removed in vacuo the residue purified by flash chromatography