N-phenylmethoxymethanamine

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: 3-(Methylthio)phenyl isocyanate (2.0 g, 12 mmol) was added dropwise to a solution of N-benzyloxy-N-methylamine (1.55 g, 11.3 mmol) in tetrahydrofuran (25 mL). The reaction mixture was stirred at ambient temperature for 2 hours then concentrated under vacuum. The residue was purified by flash chromatography (silica gel; ethyl acetate:hexanes) to provide 3.26 g of 1-benzyloxy-1-methyl-3-[3(methylthio)phenyl]urea as an oil. then concentrated under vacuum The residue was purified by flash chromatography (silica gel; ethyl acetate:hexanes)

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

実験手順: Using the general method of Compound 54 Part C, tert-butyl N-benzyloxy-N-methylcarbamate (3.0 g, 13 mmol) was reacted with trifluoroacetic acid (10 mL, 130 mmol) to provide 1.58 g of N-benzyloxy-N-methylamine as a yellow oil.

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

実験手順: Using the general method of Compound 54 Part C, tert-butyl N-benzyloxy-N-methylcarbamate (3.0 g, 13 mmol) was reacted with trifluoroacetic acid (10 mL, 130 mmol) to provide 1.58 g of N-benzyloxy-N-methylamine as a yellow oil.

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

実験手順: 2-Chloro-N-(4,6-bis-(n-propylamino)-[1,3,5]triazine (XXXIV) and O-benzyl-N-methyl-hydroxylamine (LII) were reacted as described in Example 13 to yield O-benzyl-N-(4,6-bis-propylamino-[1,3,5]triazin-2-yl)-N-methyl-hydroxylamine (LIII) (29% yield). 200 MHz 1H NMR (DMSO-d6, ppm) 7.52-7.28 (5H, m), 7.07-6.67 (2H, m), 4.93 (2H, s), 3.26-3.03 (7H, m), 1.58-1.39 (4H, m), 0.85 (6H, t, J=7.2 Hz). ESI-MS (m/z): 331 [M+H]+.

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

実験手順: A 1M HCl/EtOH solution (50 mL) was added dropwise to the solution of formaldehyde O-benzyl-oxime (3.85 g, 28.48 mmol) in EtOH at 0° C. The mixture was stirred at room temperature for 1 hour, volatiles were removed in vacuo. The residue was dissolved in dichloromethane (100 mL), washed with saturated NaHCO3 solution (75 mL), water (75 mL), and dried over Na2SO4. The product was purified by flash column chromatography using gradient elution from petroleum ether/EtOAc (9:1) to petroleum ether/EtOAc (7:1) to yield O-benzyl-N-methyl-hydroxylamine (1.72 g, 44%). 200 MHz 1H NMR (CDCl3, ppm) 7.40-7.27 (5H, m), 5.53 (1H, br s), 4.71 (2H, s), 2.73 (3H, s). volatiles were removed in vacuo The residue was dissolved in dichloromethane (100 mL) washed with saturated NaHCO3 solution (75 mL), water (75 mL) dried over Na2SO4 The product was purified by flash column chromatography elution from petroleum ether/EtOAc (9:1) to petroleum ether/EtOAc (7:1)

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

実験手順: A 1M HCl/EtOH solution (50 mL) was added dropwise to the solution of formaldehyde O-benzyl-oxime (3.85 g, 28.48 mmol) in EtOH at 0° C. The mixture was stirred at room temperature for 1 hour, volatiles were removed in vacuo. The residue was dissolved in dichloromethane (100 mL), washed with saturated NaHCO3 solution (75 mL), water (75 mL), and dried over Na2SO4. The product was purified by flash column chromatography using gradient elution from petroleum ether/EtOAc (9:1) to petroleum ether/EtOAc (7:1) to yield O-benzyl-N-methyl-hydroxylamine (1.72 g, 44%). 200 MHz 1H NMR (CDCl3, ppm) 7.40-7.27 (5H, m), 5.53 (1H, br s), 4.71 (2H, s), 2.73 (3H, s). volatiles were removed in vacuo The residue was dissolved in dichloromethane (100 mL) washed with saturated NaHCO3 solution (75 mL), water (75 mL) dried over Na2SO4 The product was purified by flash column chromatography elution from petroleum ether/EtOAc (9:1) to petroleum ether/EtOAc (7:1)

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-Chloro-N-(4,6-bis-(n-propylamino)-[1,3,5]triazine (XXXIV) and O-benzyl-N-methyl-hydroxylamine (LII) were reacted as described in Example 13 to yield O-benzyl-N-(4,6-bis-n-propylamino-[1,3,5]triazin-2-yl)-N-methyl-hydroxylamine (LIII) (29% yield). 200 MHz 1H NMR (DMSO-d6, ppm) 7.52-7.28 (5H, m), 7.07-6.67 (2H, m), 4.93 (2H, s), 3.26-3.03 (7H, m), 1.58-1.39 (4H, m), 0.85 (6H, t, J=7.2 Hz). ESI-MS (m/z): 331 [M+H]+.

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

実験手順: A 1M HCl/EtOH solution (50 mL) was added dropwise to the solution of formaldehyde O-benzyl-oxime (3.85 g, 28.48 mmol) in EtOH at 0° C. The mixture was stirred at room temperature for 1 hour, volatiles were removed in vacuo. The residue was dissolved in dichloromethane (100 mL), washed with saturated NaHCO3 solution (75 mL), water (75 mL), and dried over Na2SO4. The product was purified by flash column chromatography using gradient elution from petroleum ether/EtOAc (9:1) to petroleum ether/EtOAc (7:1) to yield O-benzyl-N-methyl-hydroxylamine (1.72 g, 44%). 200 MHz 1H NMR (CDCl3, ppm) 7.40-7.27 (5H, m), 5.53 (1H, br s), 4.71 (2H, s), 2.73 (3H, s). volatiles were removed in vacuo The residue was dissolved in dichloromethane (100 mL) washed with saturated NaHCO3 solution (75 mL), water (75 mL) dried over Na2SO4 The product was purified by flash column chromatography elution from petroleum ether/EtOAc (9:1) to petroleum ether/EtOAc (7:1)

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

実験手順: 151 (616 mg) was dissolved in 4 ml of DCM and 4 ml of TFA was added then the reaction mixture was let 1 h at room temperature. The reaction mixture is concentrated and 50 ml of AcOEt are added. The organic phase are washed with saturated NaHCO3 and brine then dried over Na2SO4, filtered and concentrated to afford 152 as an oil (324 mg, 88%). 1H NMR (DMSO): δ 0.99 (t, 3H, J=7.3 Hz), 2.82 (m, 2H), 4.61 (s, 2H), 6.50 (t, 1H, J=5.8 Hz), 7.32 (m, 5H). The reaction mixture is concentrated 50 ml of AcOEt are added The organic phase are washed with saturated NaHCO3 and brine then dried over Na2SO4 filtered concentrated

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

実験手順: To a stirred solution of O-benzylhydroxyl amine hydrochloride (1.59 g, 10 mmole) in 15 ml of dry HMPA containing dry sodium bicarbonate (3.36 g, 40 mmole) was added methyl iodide (1.5 g, 11 mmole). After 5 hours the resulting mixture was diluted with 30 ml of water and 20 ml of brine and extracted three times with ethyl ether. The extracts were combined, washed, dried and evaporated to produce the crude product as an oil. The oil was chromatographed to afford 800 mg of title C compound, with consistent spectral data. extracted three times with ethyl ether washed dried evaporated