2H-Pyran-4-carboxylicacid,4-aminotetrahydro-,methylester(9CI)

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Methyl-4-nitroaniline was converted to the 2-methyl-4-nitroformanilide according to Method A3a, Step 1. The formanilide was converted to 2-methyl-4-nitrophenyl isocyanide dichloride according to Method A3a, Step 2. 4-Aminotetrahydro-2H-pyran4-carboxylic acid was converted to the methyl ester according to Method B1b, Step 1. Methyl 4-aminotetrahydro-2H-pyran-4-carboxylate was reduced to 4-amino-4-(hydroxymethyl)tetrahydro-2H-pyran according to Method B1b, Step 2. The 2-hydroxyethylamine was reacted with isobutyraldehyde according to Method B4c, Step 1 to afford 2-isopropyl-1-aza-3,8-dioxaspiro[4.5]decane. The oxazolidine was reduced to 4-isobutylamino-4-(hydroxymethyl)tetrahydro-2H-pyran. The substituted 2-hydroxyethylamine was converted to 4-isobutylamino-4-(acetylthiomethyl)tetrahydro-2H-pyran according to Method C6c, Step 1. The thioacetate was saponified according to Method C6c, Step 2 to give 4-isobutylamino-4-(thiomethyl)tetrahydro-2H-pyran. The 2-thioethylamine was reacted with 2-methyl-4-nitrophenyl isocyanide dichloride to afford 2-(2-methyl-4-nitrophenylimino-1-isobutyl-1-aza-8-oxa-3-thiaspiro[4.5]decane.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Methyl-4-nitroaniline was converted to the 2-methyl-4-nitroformanilide according to Method A3a, Step 1. The formanilide was converted to 2-methyl-4-nitrophenyl isocyanide dichloride according to Method A3a, Step 2. 4-Aminotetrahydro-2H-pyran4-carboxylic acid was converted to the methyl ester according to Method B1b, Step 1. Methyl 4-aminotetrahydro-2H-pyran-4-carboxylate was reduced to 4-amino-4-(hydroxymethyl)tetrahydro-2H-pyran according to Method B1b, Step 2. The 2-hydroxyethylamine was reacted with isobutyraldehyde according to Method B4c, Step 1 to afford 2-isopropyl-1-aza-3,8-dioxaspiro[4.5]decane. The oxazolidine was reduced to 4-isobutylamino-4-(hydroxymethyl)tetrahydro-2H-pyran. The substituted 2-hydroxyethylamine was converted to 4-isobutylamino-4-(acetylthiomethyl)tetrahydro-2H-pyran according to Method C6c, Step 1. The thioacetate was saponified according to Method C6c, Step 2 to give 4-isobutylamino-4-(thiomethyl)tetrahydro-2H-pyran. The 2-thioethylamine was reacted with 2-methyl-4-nitrophenyl isocyanide dichloride to afford 2-(2-methyl-4-nitrophenylimino-1-isobutyl-1-aza-8-oxa-3-thiaspiro[4.5]decane.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Methyl-4-nitroaniline was converted to the 2-methyl-4-nitroformanilide according to Method A3a, Step 1. The formanilide was converted to 2-methyl-4-nitrophenyl isocyanide dichloride according to Method A3a, Step 2. 4-Aminotetrahydro-2H-pyran4-carboxylic acid was converted to the methyl ester according to Method B1b, Step 1. Methyl 4-aminotetrahydro-2H-pyran-4-carboxylate was reduced to 4-amino-4-(hydroxymethyl)tetrahydro-2H-pyran according to Method B1b, Step 2. The 2-hydroxyethylamine was reacted with isobutyraldehyde according to Method B4c, Step 1 to afford 2-isopropyl-1-aza-3,8-dioxaspiro[4.5]decane. The oxazolidine was reduced to 4-isobutylamino-4-(hydroxymethyl)tetrahydro-2H-pyran. The substituted 2-hydroxyethylamine was converted to 4-isobutylamino-4-(acetylthiomethyl)tetrahydro-2H-pyran according to Method C6c, Step 1. The thioacetate was saponified according to Method C6c, Step 2 to give 4-isobutylamino-4-(thiomethyl)tetrahydro-2H-pyran. The 2-thioethylamine was reacted with 2-methyl-4-nitrophenyl isocyanide dichloride to afford 2-(2-methyl-4-nitrophenylimino-1-isobutyl-1-aza-8-oxa-3-thiaspiro[4.5]decane.

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution 4-aminotetrahydro-2H-pyran-4-carboxylic acid (0.50 g, 3.4 mmol) in MeOH (10 mL) was saturated with HCl gas at 0-5° C., and the mixture was then heated at reflux for 3.5 h. The solvents were evaporated in vacuo, the residue was dissolved in saturated aqueous NaHCO3 and the aqueous solution was extracted with CH2Cl2 (2×50 mL). The combined extracts were dried (MgSO4) and evaporated in vacuo to give methyl 4-aminotetrahydro-2H-pyran-4-carboxylate (410 mg, 2.58 mmol). the mixture was then heated at reflux for 3.5 h The solvents were evaporated in vacuo the residue was dissolved in saturated aqueous NaHCO3 the aqueous solution was extracted with CH2Cl2 (2×50 mL) The combined extracts were dried (MgSO4) evaporated in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 4-amino-4-carboxy-tetrahydropyrane hydrochloride (2 g) in methanol was added dropwise a solution of 2M trimethylsilyldiazomethane-diethylether (33 mL) under ice-cooling, and the mixture was stirred at room temperature for 4 days. The reaction mixture was concentrated in vacuo, and the resultant crude product was dissolved in hexane-diethylether (1 mL/1 mL), and thereto was added an aqueous 4N hydrochloric acid. The precipitates were collected by filtration to give 4-amino-4-methoxycarbonyl-tetrahydropyrane (2.13 g, yield: 99%) as white-crystals. cooling The reaction mixture was concentrated in vacuo the resultant crude product was dissolved in hexane-diethylether (1 mL/1 mL) was added an aqueous 4N hydrochloric acid The precipitates were collected by filtration

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 4-amino-4-carboxy-tetrahydropyrane hydrochloride (2 g) in methanol was added dropwise a solution of 2M trimethylsilyldiazomethane-diethylether (33 mL) under ice-cooling, and the mixture was stirred at room temperature for 4 days. The reaction mixture was concentrated in vacuo, and the resultant crude product was dissolved in hexane-diethylether (1 mL/1 mL), and thereto was added an aqueous 4N hydrochloric acid. The precipitates were collected by filtration to give 4-amino-4-methoxycarbonyl-tetrahydropyrane (2.13 g, yield: 99%) as white crystals. cooling The reaction mixture was concentrated in vacuo the resultant crude product was dissolved in hexane-diethylether (1 mL/1 mL) was added an aqueous 4N hydrochloric acid The precipitates were collected by filtration

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Methyl-4-nitroaniline was converted to the 2-methyl-4-nitroformanilide according to Method A3a, Step 1. The formanilide was converted to 2-methyl-4-nitrophenyl isocyanide dichloride according to Method A3a, Step 2. 4-Aminotetrahydro-2H-pyran4-carboxylic acid was converted to the methyl ester according to Method B1b, Step 1. Methyl 4-aminotetrahydro-2H-pyran-4-carboxylate was reduced to 4-amino-4-(hydroxymethyl)tetrahydro-2H-pyran according to Method B1b, Step 2. The 2-hydroxyethylamine was reacted with isobutyraldehyde according to Method B4c, Step 1 to afford 2-isopropyl-1-aza-3,8-dioxaspiro[4.5]decane. The oxazolidine was reduced to 4-isobutylamino-4-(hydroxymethyl)tetrahydro-2H-pyran. The substituted 2-hydroxyethylamine was converted to 4-isobutylamino-4-(acetylthiomethyl)tetrahydro-2H-pyran according to Method C6c, Step 1. The thioacetate was saponified according to Method C6c, Step 2 to give 4-isobutylamino-4-(thiomethyl)tetrahydro-2H-pyran. The 2-thioethylamine was reacted with 2-methyl-4-nitrophenyl isocyanide dichloride to afford 2-(2-methyl-4-nitrophenylimino-1-isobutyl-1-aza-8-oxa-3-thiaspiro[4.5]decane.