2-methylpropanamide

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:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: tert-Butyl (3S)-1-(1-(3-(7-bromo quinolin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)-2,2,2-trifluoroethyl)pyrrolidin-3-ylcarbamate (50 mg, 0.085 mmol), isobutyramide (18.4 mg, 0.211 mmol), K3PO4 (53.8 mg, 0.254 mmol), and Cu(I)I (1.61 mg, 0.0085 mmol) were weighed into a 40 mL Teflon® capped vial. The vial was purged with N2, followed by addition of toluene (20 mL) and N1,N2-dimethylethane-1,2-diamine (4.55 μL, 0.042 mmol). The reaction was sealed and heated to 90° C. overnight, after which the reaction complete by TLC. The crude reaction was concentrated, then purified by flash column chromatography (eluting with 10% MeOH/DCM), affording the desired product (55 mg, 97% yield). capped vial The vial was purged with N2 The reaction was sealed after which the reaction complete by TLC The crude reaction was concentrated purified by flash column chromatography (eluting with 10% MeOH/DCM)

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

Procedure: A 250 ml, three-necked, round bottom flask, was equipped with a condenser, drying tube, mechanical stirrer, gas inlet tube, thermometer and heating mantle. Toluene (100 ml) was introduced and hydrogen chloride gas was bubbled through the solvent until the solution was saturated. Isobutyramide (8.70 g, 0.10 mole) was added and the mixture was heated to 92°. Diketene (8.40 g, 0.10 mole) was added over a 6 minute period and after heating for 15 minutes, a 38.7% yield of N-acetoacetylisobutyramide was obtained. A 250 ml, three-necked, round bottom flask, was equipped with a condenser drying tube, mechanical stirrer, gas inlet tube thermometer and heating mantle Toluene (100 ml) was introduced hydrogen chloride gas was bubbled through the solvent until the solution the mixture was heated to 92° after heating for 15 minutes

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

Procedure: Isobutyramide (8.7 g, 0.1 mole), pyridine (0.40 g, 0.005 mole), pyridine hydrochloride (1.73 g, 0.015 mole), diketene (8.4 g, 0.1 mole) and trichloroethylene (100 ml) were placed in a 250 ml, 3-neck flask equipped with a magnetic stirrer, a thermometer, a condenser, a drying tube and a heating mantle. The mixture was slowly heated to 80°, and the temperature range of 75°-81° was maintained for 1 hour. The slightly cooled reaction mixture was poured into a 500 ml, r.b. flask and the solvent was stripped off to give an orange oil. Crude N-acetoacetylisobutyramide thus obtained was dissolved in toluene (100 ml) and placed in a 250 ml, 3-neck flask equipped similarly as in Example 1. After addition of acetic acid (3 g, 0.05 mole), ammonia gas was bubbled in as the reaction mixture was heated at reflux for 1 hour and was further refluxed for 1 hour after the ammonia was turned off. Chloroform (~50 ml) was added to the cooled reaction mixture and the insoluble solid was filtered and washed with chloroform (~ 50 ml). The solvent of the filtrate was stripped off and 15.51 g (81.9%, by weight, of oxypyrimidine) of yellow crystals having m.p. 148°-160° were obtained. The yield was 83.6%. equipped with a magnetic stirrer The mixture was slowly heated to 80° the temperature range of 75°-81° was maintained for 1 hour The slightly cooled reaction mixture was poured into a 500 ml flask and the solvent was stripped off to give an orange oil

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

Procedure: In substantially the same manner as in Reference Example 31, isobutyramide was allowed to react with 1,3-dichloroacetone to give 4-chloromethyl-2-isopropyl oxazole as an oily product. The yield was 6.2%.

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

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

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

Procedure: 1-[8-Bromo-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]-2-methylpropan-2-ol (0.550 g, 1.45 mmol), isobutyramide (0.150 g, 1.74 mmol), copper(I) iodide (0.055 g, 0.290 mmol), potassium phosphate (0.647 g, 3.05 mmol), and 1,4-dioxane (1.5 mL) were added to a scintillation vial. 1,2-(±)-trans-Diaminocyclohexane (0.035 mL, 0.290 mmol) was added. The vial was flushed with nitrogen, sealed with a Teflon-lined cap and heated at 110° C. for 72 hours. The vial was cooled to ambient temperature and the reaction was diluted with dichloromethane and methanol. Purification by chromatography with a HORIZON HPFC system (silica cartridge, eluting with a linear gradient of 1-15% CMA in chloroform) provided 0.38 g of N-[2-(ethoxymethyl)-1-(2-hydroxy-2-methylpropyl)-1H-imidazo[4,5-c]quinolin-8-yl]-2-methylpropanamide as a dark semi-solid. The vial was flushed with nitrogen sealed with a Teflon- lined cap The vial was cooled to ambient temperature the reaction was diluted with dichloromethane and methanol Purification by chromatography with a HORIZON HPFC system (silica cartridge eluting with a linear gradient of 1-15% CMA in chloroform)