1,3-dioxolan-2-ylmethanamine

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

Procedure: To a solution of 0.50 g of 2,6-dichloro-3-nitropyridine in 5 mL of acetonitrile, 0.43 g of potassium carbonate was added, thereto was added a solution of 0.24 mL of 2-aminomethyl-1,3-dioxolan in 3 mL of acetonitrile under cooling with ice, and the mixture was stirred for 2 hours under cooling with ice. Thereto was further added 80 μL of 2-aminomethyl-1,3-dioxolan, and the mixture was stirred for 2 hours under cooling with ice. Water and ethyl acetate were added thereto under cooling with ice, the organic layer was separated, washed with a saturated aqueous sodium chloride solution and dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The resultant residue was purified by basic silica gel column chromatography using an eluent of hexane:ethyl acetate=20:1 to obtain 0.44 g of 6-chloro-N-(1,3-dioxolan-2-ylmethyl)-3-nitropyridin-2-amine as a yellow solid. under cooling with ice under cooling with ice the mixture was stirred for 2 hours under cooling with ice under cooling with ice the organic layer was separated washed with a saturated aqueous sodium chloride solution dried over anhydrous sodium sulfate the solvent was distilled off under reduced pressure The resultant residue was purified by basic silica gel column chromatography

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

Procedure: To a solution of 1.1 g of 1-(1,3-dioxolan-2-yl)methanamine in 10 mL of N,N-dimethylformamide, 1.6 mL of triethylamine and 2.0 g of 2-chloro-6-methoxy-3-nitropyridine were added at room temperature, and the mixture was stirred at 55 to 65° C. for 1 hour. The reaction mixture was cooled to room temperature, and ethyl acetate and water were then added thereto. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The organic layer and the extract were combined, the resultant solution was washed sequentially with water and a saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain 2.7 g of N-(1,3-dioxolan-2-ylmethyl)-6-methoxy-3-nitropyridin-2-amine as a yellow solid. The reaction mixture was cooled to room temperature The organic layer was separated the aqueous layer was extracted with ethyl acetate the resultant solution was washed sequentially with water a saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate the solvent was distilled off under reduced pressure

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 DCM solution of 1-(1,3-dioxolan-2-yl)methanamine (799 mg, 7.83 mmol) was added 2-(chloromethyl)imidazo[1,2-a]pyridine-7-carbonitrile hydrochloride (Intermediate 17) (500 mg, 2.61 mmol). After heating to reflux for 1 hr, the reaction mixture was cooled room temperature, concentrated under reduced pressure, chromatographed on silica gel eluting with a gradient solvent mixture (5% MeOH-DCM to 15% MeOH-DCM) to give the title compound as oil (410 mg). LC/MS: m/z 259(M+H). After heating to reflux for 1 hr concentrated under reduced pressure chromatographed on silica gel eluting with a gradient solvent mixture (5% MeOH-DCM to 15% MeOH-DCM)

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

Procedure: To a DCM 5 mL solution of 1-(1,3-dioxolan-2-yl)methanamine (814 mg, 7.89 mmol) was added 2-(chloromethyl)-7-(trifluoromethyl)imidazo[1,2-a]pyridine (Intermediate 19) (620 mg, 2.63 mmol). After heating to reflux for 1.5 hr, the reaction mixture (suspension) was cooled to room temperature and concentrated under reduced pressure. The residue was chromatographed on silica gel eluting with a gradient solvent mixture (5% MeOH-DCM to 15% MeOH-DCM) to give the title compound as solid (450 mg). LC/MS: m/z 302(M+H). After heating to reflux for 1.5 hr concentrated under reduced pressure The residue was chromatographed on silica gel eluting with a gradient solvent mixture (5% MeOH-DCM to 15% MeOH-DCM)

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

Procedure: To a DCM 5 mL solution of 1-(1,3-dioxolan-2-yl)methanamine (814 mg, 7.89 mmol) was added 2-(chloromethyl)-7-(trifluoromethyl)imidazo[1,2-a]pyridine (Intermediate 19) (620 mg, 2.63 mmol). After heating to reflux for 1.5 hr, the reaction mixture (suspension) was cooled to room temperature and concentrated under reduced pressure. The residue was chromatographed on silica gel eluting with a gradient solvent mixture (5% MeOH-DCM to 15% MeOH-DCM) to give the title compound as solid (450 mg). LC/MS: m/z 302(M+H). After heating to reflux for 1.5 hr concentrated under reduced pressure The residue was chromatographed on silica gel eluting with a gradient solvent mixture (5% MeOH-DCM to 15% MeOH-DCM)