tert-butyl 2-methylsulfanyl-4,5-dihydroimidazole-1-carboxylate

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

Conditions: temp:35.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 3-amino-5-trifluoromethylhippuric acid hydrochloride [prepared according to Example M, Steps A and B substituting 3-nitro-5-trifluoromethylbenzoyl chloride (prepared from 3-nitro-5-trifluoromethylbenzoic acid (Lancaster) and thionyl chloride for M-nitrobenzoyl chloride in Example M, Step A] (3 g, 0.01 mole) in CH3CN (5 mL) was added the product from Example 472, Step A (2.2 g, 0.01 mole). The reaction was stirred at 35° C. for 3 days then at reflux for 4 hours. After cooling, the CH3CN was decanted off, the residue slurried several times in ether (ether decanted off) and then dried to yield 3-(4,5-dihydro-1H-imidazol-2-yl)amino-5-trifluoromethylhippuric acid.HCl (2.5 g) as a white solid. at reflux for 4 hours After cooling the CH3CN was decanted off dried

Conditions: temp:35.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 3-amino-5-trifluoromethylhippuric acid hydrochloride [prepared according to Example M, Steps A and B substituting 3-nitro-5-trifluoromethylbenzoyl chloride (prepared from 3-nitro-5-trifluoromethylbenzoic acid (Lancaster) and thionyl chloride for M-nitrobenzoyl chloride in Example M, Step A] (3 g, 0.01 mole) in CH3CN (5 mL) was added the product from Example 472, Step A (2.2 g, 0.01 mole). The reaction was stirred at 35° C. for 3 days then at reflux for 4 hours. After cooling, the CH3CN was decanted off, the residue slurried several times in ether (ether decanted off) and then dried to yield 3-(4,5-dihydro-1H-imidazol-2-yl)amino-5-trifluoromethylhippuric acid.HCl (2.5 g) as a white solid. at reflux for 4 hours After cooling the CH3CN was decanted off dried

Conditions: temp:35.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 3-amino-5-trifluoromethylhippuric acid hydrochloride [prepared according to Example M, Steps A and B substituting 3-nitro-5-trifluoromethylbenzoyl chloride (prepared from 3-nitro-5-trifluoromethylbenzoic acid (Lancaster) and thionyl chloride for M-nitrobenzoyl chloride in Example M, Step A] (3 g, 0.01 mole) in CH3CN (5 mL) was added the product from Example 472, Step A (2.2 g, 0.01 mole). The reaction was stirred at 35° C. for 3 days then at reflux for 4 hours. After cooling, the CH3CN was decanted off, the residue slurried several times in ether (ether decanted off) and then dried to yield 3-(4,5-dihydro-1H-imidazol-2-yl)amino-5-trifluoromethylhippuric acid.HCl (2.5 g) as a white solid. at reflux for 4 hours After cooling the CH3CN was decanted off dried

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

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 6-amino-5-methyl-4-(4-phenoxy-phenylamino)-pyrrolo[1,2-b]pyridazine-3-carbonitrile hydrochloride (Example 11) (49 mg, 0.125 mmol) and 2-methylsulfanyl-4,5-dihydro-imidazole-1-carboxylic acid tert-butyl ester (25.5 mg, 0.125 mmol) in MeOH (2 ml) was heated at 70° C. for 3 h, then cooled to rt and stirred overnight. The reaction mixture was diluted with CHCl3 (25 ml), washed with saturated NaHCO3 (10 ml) dried with Na2SO4. Concentrated in vacuo and purified by prep. TLC to give 424A (22 mg, 97%) as pale yellow flakes (5% MeOH—CHCl3). It has a retention time of 6.82 min (standard LC1 method, 8 min run). MS Found: (M+M)+=523.9 cooled to rt washed with saturated NaHCO3 (10 ml) dried with Na2SO4 Concentrated in vacuo purified by prep

Conditions: temp:35.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 3-amino-5-trifluoromethylhippuric acid hydrochloride [prepared according to Example M, Steps A and B substituting 3-nitro-5-trifluoromethylbenzoyl chloride (prepared from 3-nitro-5-trifluoromethylbenzoic acid (Lancaster) and thionyl chloride for M-nitrobenzoyl chloride in Example M, Step A] (3 g, 0.01 mole) in CH3CN (5 mL) was added the product from Example 472, Step A (2.2 g, 0.01 mole). The reaction was stirred at 35° C. for 3 days then at reflux for 4 hours. After cooling, the CH3CN was decanted off, the residue slurried several times in ether (ether decanted off) and then dried to yield 3-(4,5-dihydro-1H-imidazol-2-yl)amino-5-trifluoromethylhippuric acid.HCl (2.5 g) as a white solid. at reflux for 4 hours After cooling the CH3CN was decanted off dried