ethylthiourea

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

Procedure: 18 Grams of N-ethyl-thiourea were dissolved in 50 m. of glacial acetic acid, boiled to reflux and treated dropwise with 17.2 g of diketene. The mixture was then boiled at reflux for 20 minutes and subsequently evaporated to 50 ml. While cooling and stirring, the residue was treated with 50 ml of water. The yellowish crystals which precipitated were filtered off under suction and recrystallized from tetrahydrofuran to give 1-ethyl-1,4-dihydro-2-mercapto-6-methyl-4-oxo-pyrimidine; melting point 190°. to reflux at reflux for 20 minutes subsequently evaporated to 50 ml While cooling the residue was treated with 50 ml of water The yellowish crystals which precipitated were filtered off under suction recrystallized from tetrahydrofuran

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

Procedure: 18 Grams of N-ethyl-thiourea were dissolved in 50 m. of glacial acetic acid, boiled to reflux and treated dropwise with 17.2 g of diketene. The mixture was then boiled at reflux for 20 minutes and subsequently evaporated to 50 ml. While cooling and stirring, the residue was treated with 50 ml of water. The yellowish crystals which precipitated were filtered off under suction and recrystallized from tetrahydrofuran to give 1-ethyl-1,4-dihydro-2-mercapto-6-methyl-4-oxo-pyrimidine; melting point 190°. to reflux at reflux for 20 minutes subsequently evaporated to 50 ml While cooling the residue was treated with 50 ml of water The yellowish crystals which precipitated were filtered off under suction recrystallized from tetrahydrofuran

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

Procedure: The reaction described in Preparation 42 was repeated but using 10 g of ethylthiourea, 20 g of ethyl bromopyruvate and 100 ml of ethanol, giving the title compound as a pale yellow powder. The reaction described in Preparation 42

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

Procedure: 18 Grams of N-ethyl-thiourea were dissolved in 50 m. of glacial acetic acid, boiled to reflux and treated dropwise with 17.2 g of diketene. The mixture was then boiled at reflux for 20 minutes and subsequently evaporated to 50 ml. While cooling and stirring, the residue was treated with 50 ml of water. The yellowish crystals which precipitated were filtered off under suction and recrystallized from tetrahydrofuran to give 1-ethyl-1,4-dihydro-2-mercapto-6-methyl-4-oxo-pyrimidine; melting point 190°. to reflux at reflux for 20 minutes subsequently evaporated to 50 ml While cooling the residue was treated with 50 ml of water The yellowish crystals which precipitated were filtered off under suction recrystallized from tetrahydrofuran

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

Procedure: To a solution of 2-bromo-1-(4-fluorophenyl)-2-(4-methylsulfonylphenyl)ethanone (Example 26, Step 2) (0.405 g, 1.09 mmol) in ethanol (10 mL) in a 25 mL round bottom flask was added N-ethylthiourea (0.114 g, 1.09 mmol) and the solution was heated to reflux for 14 hours. The reaction was cooled to room temperature and the resulting suspension was concentrated in vacuo, suspended in methylene chloride (100 mL) and washed with NaHCO3 saturated solution (3×10 mL), sodium carbonate solution (10%, 3×20 mL), dried over sodium sulfate, filtered and concentrated. The crude product was recrystallized from methylene chloride and isooctane yielding 2-ethylamino-4-(4-fluorophenyl)-5-(4-methylsulfonylphenyl)thiazole (0.218 g, 53%) as a white powdery crystals: mp 218°-219° C., 1HNMR (DMSO d6) 400 mHz 7.94 (t, 5.38 Hz, 1 H), 7.78 (d, J=8.56 Hz, 2 H), 7.45-7.40 (m, 2 H), 7.37 (d, J=8.56 Hz, 2 H), 7.15 (t, J=9.05 Hz, 2 H), 3.31 (q, J=7.10 Hz, 2 H), 3.18 (s, 3 H), 1.18 (t, J=7.10 Hz, 3 H); MS m/z 377 (M+H). HRMS Δ=0.5 mmu. the solution was heated to reflux for 14 hours the resulting suspension was concentrated in vacuo washed with NaHCO3 saturated solution (3×10 mL), sodium carbonate solution (10%, 3×20 mL) dried over sodium sulfate filtered concentrated The crude product was recrystallized from methylene chloride and isooctane

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-(3-bromoacetyl-phenyl)-8-chloro-7-dimethylamino-1,3-dihydro-benzo[b][1,4]diazepin-2-one (130 mg) (Example 193a) and N-ethyl-thiourea (31 mg) in THF (3 mL) was heated at 60° C. for 15 min. The mixture was diluted with AcOEt and washed with sat. NaHCO3 solution and with brine. The organic layer was dried and evaporated and the residue was purified by chromatography on silica gel using AcOEt/hexane (1:1) as eluent. The purified product was triturated with Et2O to give the title compound (24 mg) as yellow solid. washed with sat. NaHCO3 solution and with brine The organic layer was dried evaporated the residue was purified by chromatography on silica gel The purified product was triturated with Et2O

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

Procedure: To 36 g. of 1-ethylthiourea in 200 ml. of acetone was added 70 g. of methyliodide. Evaporation of the solvent gave 71 g. of 1-ethyl-2-methylisothiourea hydroiodide as colorless crystals, m.p. 84°-87° C. This isothiurea, 23.2 g., was reacted with a total of 30 ml. of benzoyl chloride and after 6 hours the solution was poured onto ice. The mixture was made basic with NaOH and the crystals which formed were collected by filtration to give 27.8 g. of 1,3-bisbenzoyl-1-ethyl-2-methylisothiourea, m.p. 84°-86° C. This bisbenzoylisothiourea, 3.1 g., was reacted with 2.4 g. of 4-aminomethylbenzenesulfonamide hydrochloride and 1.5 g. of sodium acetate in 250 ml. of isopropyl alcohol. Aqueous work-up followed by dichloromathane extraction and evaporation gave the title compound as a colorless glass, m.p. 70°-80° C. Evaporation of the solvent gave 71 g , was reacted with a total of 30 ml the crystals which formed were collected by filtration to give 27.8 g , was reacted with 2.4 g Aqueous work-up followed by dichloromathane extraction and evaporation

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

Procedure: 18 Grams of N-ethyl-thiourea were dissolved in 50 m. of glacial acetic acid, boiled to reflux and treated dropwise with 17.2 g of diketene. The mixture was then boiled at reflux for 20 minutes and subsequently evaporated to 50 ml. While cooling and stirring, the residue was treated with 50 ml of water. The yellowish crystals which precipitated were filtered off under suction and recrystallized from tetrahydrofuran to give 1-ethyl-1,4-dihydro-2-mercapto-6-methyl-4-oxo-pyrimidine; melting point 190°. to reflux at reflux for 20 minutes subsequently evaporated to 50 ml While cooling the residue was treated with 50 ml of water The yellowish crystals which precipitated were filtered off under suction recrystallized from tetrahydrofuran