4-(aminomethyl)oxan-4-ol

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: 4-Aminomethyl-tetrahydro-pyran-4-ol is prepared from 1,6-dioxa-spiro[2.5]octane. A MeOH (3.5 mL) solution of 1,6-dioxa-spiro[2.5]octane (0.19 g, 1.7 mmol) is added to concentrated aqueous NH4OH (4.3 mL) at 0° C. The reaction mixture is warmed to room temperature and stirred for 16 hours. The reaction mixture is concentrated under reduced pressure and purified by column chromatography (10% MeOH, 2% Et3N in DCM) to afford 90 mg (41%) of the desired product as a white solid. The reaction mixture is concentrated under reduced pressure purified by column chromatography (10% MeOH, 2% Et3N in DCM)

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

Procedure: 4-Aminomethyl-tetrahydro-pyran-4-ol is prepared from 1,6-dioxa-spiro[2.5]octane. A MeOH (3.5 mL) solution of 1,6-dioxa-spiro[2.5]octane (0.19 g, 1.7 mmol) is added to concentrated aqueous NH4OH (4.3 mL) at 0° C. The reaction mixture is warmed to room temperature and stirred for 16 hours. The reaction mixture is concentrated under reduced pressure and purified by column chromatography (10% MeOH, 2% Et3N in DCM) to afford 90 mg (41%) of the desired product as a white solid. The reaction mixture is concentrated under reduced pressure purified by column chromatography (10% MeOH, 2% Et3N in DCM)

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

Procedure: The methanol solution of 1,6-dioxaspiro[2.5]octane (3.15 g, 27.6 mmol) was added to the 25% ammonia aqueous solution (50.0 mL, 27.6 mmol) at 0° C. The mixture was warmed to room temperature and stirred for 18 h. The reaction mixture was concentrated in vacuo. The crude product was used for next step reaction without purification. The reaction mixture was concentrated in vacuo The crude product was used for next step reaction without purification

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

Procedure: The methanol solution of 1,6-dioxaspiro[2.5]octane (3.15 g, 27.6 mmol) was added to the 25% ammonia aqueous solution (50.0 mL, 27.6 mmol) at 0° C. The mixture was warmed to room temperature and stirred for 18 h. The reaction mixture was concentrated in vacuo. The crude product was used for next step reaction without purification. The reaction mixture was concentrated in vacuo The crude product was used for next step reaction without purification

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

Procedure: 4-Aminomethyl-tetrahydro-pyran-4-ol is prepared from 1,6-dioxa-spiro[2.5]octane. A MeOH (3.5 mL) solution of 1,6-dioxa-spiro[2.5]octane (0.19 g, 1.7 mmol) is added to concentrated aqueous NH4OH (4.3 mL) at 0° C. The reaction mixture is warmed to room temperature and stirred for 16 hours. The reaction mixture is concentrated under reduced pressure and purified by column chromatography (10% MeOH, 2% Et3N in DCM) to afford 90 mg (41%) of the desired product as a white solid. The reaction mixture is concentrated under reduced pressure purified by column chromatography (10% MeOH, 2% Et3N in DCM)

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

Procedure: The methanol solution of 1,6-dioxaspiro[2.5]octane (3.15 g, 27.6 mmol) was added to the 25% ammonia aqueous solution (50.0 mL, 27.6 mmol) at 0° C. The mixture was warmed to room temperature and stirred for 18 h. The reaction mixture was concentrated in vacuo. The crude product was used for next step reaction without purification. The reaction mixture was concentrated in vacuo The crude product was used for next step reaction without purification

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

Procedure: Under a nitrogen atmosphere 2,4-dichloro-5,6-dimethyl-3-nitropyridine (25 g, 113 mmol) was added to a solution of 4-(aminomethyl)tetrahydro-2H-pyran-4-ol (17 g, 130 mmol) in DMF (375 mL). Triethylamine (18 mL, 130 mmol) was added slowly and the reaction mixture was stirred at ambient temperature over the weekend. The reaction mixture was concentrated under reduced pressure and the residue was partitioned between ethyl acetate (700 mL) and saturated aqueous sodium bicarbonate (100 mL). The organic layer was washed with water (3×100 mL) and brine (50 mL), dried over magnesium sulfate, filtered, and then concentrated under reduced pressure to provide an orange solid. This material was triturated with ethyl acetate to provide 6.38 g of 4-{[(2-chloro-5,6-dimethyl-3-nitropyridin-4-yl)amino]methyl}tetrahydro-2H-pyran-4-ol as a yellow solid. An additional 4.36 g of product was recovered from the mother liquor. The reaction mixture was concentrated under reduced pressure the residue was partitioned between ethyl acetate (700 mL) and saturated aqueous sodium bicarbonate (100 mL) The organic layer was washed with water (3×100 mL) and brine (50 mL) dried over magnesium sulfate filtered concentrated under reduced pressure to provide an orange solid This material was triturated with ethyl acetate

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

Procedure: A solution of 4-chloro-3-nitro[1,5]naphthyridine (16.6 g, 79.0 mmol) in dichloromethane (250 mL) and triethylamine (14.3 mL, 102.7 mmol) was cooled to 4° C. A solution of 4-aminomethyltetrahydropyran-4-ol (11.4 g, 86.9 mmol) in dichloromethane (70 mL) was added dropwise over a period of 30 minutes. The reaction mixture was allowed to stir at ambient temperature over the weekend and then it was concentrated under reduced pressure. The residue was stirred with water (300 mL). The resulting solid was isolated by filtration, rinsed with water, and dried in a vacuum oven at 50° C. for 4 hours to provide 22.53 g of 4-[(3-nitro[1,5]naphthyridin-4-ylamino)methyl]tetrahydropyran-4-ol. it was concentrated under reduced pressure The residue was stirred with water (300 mL) The resulting solid was isolated by filtration rinsed with water dried in a vacuum oven at 50° C. for 4 hours