2-bromopropanal

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 6-aminonicotinonitrile (1.2 g, 10.1 mmol) in ethanol (80 mL) was added 2-bromopropanal (6-1) (6.9 g, 50.5 mmol). The reaction mixture was stirred at 80° C. overnight. The solution was concentrated, diluted with water (20 mL) and adjusted to PH>7 with saturated aqueous NaHCO3 solution. The precipitate was collected to afford the title compound (430 mg). MS (m/z): 158 (M+H)+. The solution was concentrated diluted with water (20 mL) The precipitate was collected

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

Procedure: 4-Amino-N,N-dicyclopropyl-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide (example 1J, 86.3 mg, 0.255 mmol) was dissolved in acetone and benzoyl isothiocyanate (37.8 μL, 0.281 mmol) was added. The reaction was stirred at room temperature for 2 h. The solvent was removed in vacuo. The residue was taken up in ethanol (1500 μL) and K2CO3 (49.3 mg, 0.357 mmol) was added. The reaction mixture was warmed to 60° C. for 3 h. 2-Bromopropanal (45.4 mg, 0.332 mmol) was added. After 3 h, additional 2-bromopropanal (˜100 mg) was added. Stirred at 60° C. for 16 h. Additional 2-bromopropanal was added and the reaction mixture was stirred at 60° C. 3 h. The ethanol was removed by concentration in vacuo. The crude residue was purified by flash chromatography using an Isco 12 g column eluting with 2-10% MeOH/CH2Cl2). Additional purification was accomplished via preparative HPLC. N,N-dicyclopropyl-6-ethyl-1-methyl-4-(5-methylthiazol-2-ylamino)-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide (20 mg, 17.47% yield) was isolated as a white solid. The solvent was removed in vacuo The reaction mixture was warmed to 60° C. for 3 h After 3 h Stirred at 60° C. for 16 h the reaction mixture was stirred at 60° C 3 h The ethanol was removed by concentration in vacuo The crude residue was purified by flash chromatography eluting with 2-10% MeOH/CH2Cl2) Additional purification

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

Procedure: 4-Amino-N,N-dicyclopropyl-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide (example 1J, 86.3 mg, 0.255 mmol) was dissolved in acetone and benzoyl isothiocyanate (37.8 μL, 0.281 mmol) was added. The reaction was stirred at room temperature for 2 h. The solvent was removed in vacuo. The residue was taken up in ethanol (1500 μL) and K2CO3 (49.3 mg, 0.357 mmol) was added. The reaction mixture was warmed to 60° C. for 3 h. 2-Bromopropanal (45.4 mg, 0.332 mmol) was added. After 3 h, additional 2-bromopropanal (˜100 mg) was added. Stirred at 60° C. for 16 h. Additional 2-bromopropanal was added and the reaction mixture was stirred at 60° C. 3 h. The ethanol was removed by concentration in vacuo. The crude residue was purified by flash chromatography using an Isco 12 g column eluting with 2-10% MeOH/CH2Cl2). Additional purification was accomplished via preparative HPLC. N,N-dicyclopropyl-6-ethyl-1-methyl-4-(5-methylthiazol-2-ylamino)-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide (20 mg, 17.47% yield) was isolated as a white solid. The solvent was removed in vacuo The reaction mixture was warmed to 60° C. for 3 h After 3 h Stirred at 60° C. for 16 h the reaction mixture was stirred at 60° C 3 h The ethanol was removed by concentration in vacuo The crude residue was purified by flash chromatography eluting with 2-10% MeOH/CH2Cl2) Additional purification

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 6-aminonicotinonitrile (1.2 g, 10.1 mmol) in ethanol (80 mL) was added 2-bromopropanal (6-1) (6.9 g, 50.5 mmol). The reaction mixture was stirred at 80° C. overnight. The solution was concentrated, diluted with water (20 mL) and adjusted to PH>7 with saturated aqueous NaHCO3 solution. The precipitate was collected to afford the title compound (430 mg). MS (m/z): 158 (M+H)+. The solution was concentrated diluted with water (20 mL) The precipitate was collected

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

Procedure: A mixture of 5.0 g (30 mmole) of 3-(acetoxymethyl)-2-pyridinamine and 4.8 g (35 mmole) of 2-bromopropanal spontaneously heated upon mixing. After cooling, the mixture was partitioned between aqueous potassium carbonate and dichloromethane. The organic phase was separated, washed with water, dried over magnesium sulfate, filtered, and concentrated in vacuo. Chromatography on silica gel (using ethanol-dichloromethane as eluent) yielded 2.3 g of 8-(acetoxymethyl)-3-methylimidazo[1,2-a]pyridine, as confirmed by the nmr and infrared spectra and by elemental analysis. [Calcd. for C11H12N2O2 : C, 64.69; H, 5.92; N, 13.72. Found: C, 63.70; H, 5.85; N, 14.24). A mixture of 2.3 g (11 mmole) of 8-(acetoxymethyl)-3-methylimidazo[1,2-a]pyridine and 1.65 g (11 mmole) of 2-mercaptobenzimidazole in 40 ml of 15% hydrogen bromide in acetic acid was heated on a steam bath. After being cooled to room temperature, the mixture was partitioned between 5% aqueous sodium hydroxide and dichloromethane. The organic layer was dried over sodium sulfate, filtered, and concentrated to an oil. Chromatography yielded 2.1 g of the title compound. Structure assignment was supported by the nmr and infrared spectra. spontaneously heated upon mixing After cooling the mixture was partitioned between aqueous potassium carbonate and dichloromethane The organic phase was separated washed with water dried over magnesium sulfate filtered concentrated in vacuo

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

Procedure: Operations similar to Production Example 1-(2) were conducted using 2-bromopropionaldehyde and 2-amino-5-nitropyridine. The solid whereupon obtained was suspended in ethyl acetate, and washed with saturated aqueous sodium hydrogencarbonate solution to provide the title compound as yellow solid. The solid whereupon obtained washed with saturated aqueous sodium hydrogencarbonate solution

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

Procedure: 2-Methyl-4-chloroaniline (1.0 mole), the diethyl acetal of 2-bromopropionaldehyde (1.0 mole) and sodium carbonate (1.0 mole) are charged into a glass reaction vessel equipped with a mechanical stirrer, thermometer and reflux condenser. The mixture is heated at a temperature of about 150°C for a period of about 24 hours. After this time the reaction mixture is cooled to room temperature and is filtered. The filtrate is then distilled under vacuum to yield the desired product the diethyl acetal of 3-(2-methyl-4-chloroanilino)propionaldehyde as the residue. equipped with a mechanical stirrer thermometer and reflux condenser After this time the reaction mixture is cooled to room temperature is filtered The filtrate is then distilled under vacuum

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

Procedure: 4-Amino-N,N-dicyclopropyl-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide (example 1J, 86.3 mg, 0.255 mmol) was dissolved in acetone and benzoyl isothiocyanate (37.8 μL, 0.281 mmol) was added. The reaction was stirred at room temperature for 2 h. The solvent was removed in vacuo. The residue was taken up in ethanol (1500 μL) and K2CO3 (49.3 mg, 0.357 mmol) was added. The reaction mixture was warmed to 60° C. for 3 h. 2-Bromopropanal (45.4 mg, 0.332 mmol) was added. After 3 h, additional 2-bromopropanal (˜100 mg) was added. Stirred at 60° C. for 16 h. Additional 2-bromopropanal was added and the reaction mixture was stirred at 60° C. 3 h. The ethanol was removed by concentration in vacuo. The crude residue was purified by flash chromatography using an Isco 12 g column eluting with 2-10% MeOH/CH2Cl2). Additional purification was accomplished via preparative HPLC. N,N-dicyclopropyl-6-ethyl-1-methyl-4-(5-methylthiazol-2-ylamino)-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide (20 mg, 17.47% yield) was isolated as a white solid. The solvent was removed in vacuo The reaction mixture was warmed to 60° C. for 3 h After 3 h Stirred at 60° C. for 16 h the reaction mixture was stirred at 60° C 3 h The ethanol was removed by concentration in vacuo The crude residue was purified by flash chromatography eluting with 2-10% MeOH/CH2Cl2) Additional purification

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 6-aminonicotinonitrile (1.2 g, 10.1 mmol) in ethanol (80 mL) was added 2-bromopropanal (6-1) (6.9 g, 50.5 mmol). The reaction mixture was stirred at 80° C. overnight. The solution was concentrated, diluted with water (20 mL) and adjusted to PH>7 with saturated aqueous NaHCO3 solution. The precipitate was collected to afford the title compound (430 mg). MS (m/z): 158 (M+H)+. The solution was concentrated diluted with water (20 mL) The precipitate was collected

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

Procedure: 4-Amino-N,N-dicyclopropyl-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide (example 1J, 86.3 mg, 0.255 mmol) was dissolved in acetone and benzoyl isothiocyanate (37.8 μL, 0.281 mmol) was added. The reaction was stirred at room temperature for 2 h. The solvent was removed in vacuo. The residue was taken up in ethanol (1500 μL) and K2CO3 (49.3 mg, 0.357 mmol) was added. The reaction mixture was warmed to 60° C. for 3 h. 2-Bromopropanal (45.4 mg, 0.332 mmol) was added. After 3 h, additional 2-bromopropanal (˜100 mg) was added. Stirred at 60° C. for 16 h. Additional 2-bromopropanal was added and the reaction mixture was stirred at 60° C. 3 h. The ethanol was removed by concentration in vacuo. The crude residue was purified by flash chromatography using an Isco 12 g column eluting with 2-10% MeOH/CH2Cl2). Additional purification was accomplished via preparative HPLC. N,N-dicyclopropyl-6-ethyl-1-methyl-4-(5-methylthiazol-2-ylamino)-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide (20 mg, 17.47% yield) was isolated as a white solid. The solvent was removed in vacuo The reaction mixture was warmed to 60° C. for 3 h After 3 h Stirred at 60° C. for 16 h the reaction mixture was stirred at 60° C 3 h The ethanol was removed by concentration in vacuo The crude residue was purified by flash chromatography eluting with 2-10% MeOH/CH2Cl2) Additional purification