tert-butyl N-(6-aminohexyl)carbamate

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: To a 0° C. stirred solution of 1.0 g (4.62 mmol) of N-Boc-1,6-diaminohexane in 30 ml ethanol was added 0.86 g (4.62 mmol) of intermediate B. After two hours the solution was concentrated, diluted with water (50 ml), and extracted with ether twice. The aqueous phase was freeze-dried to yield 0.9 g of white sticky solid tert-butyl N-(6-((acetimidoyl) amino)hexyl)carbamate intermediate. A suspension of the carbamate above (0.88 g, 3 mmol) in 15 ml dioxane and 7.5 ml trifluoroactic acid was treated with 10 ml (40 mmol) of 4N hydrochloric acid in dioxane solution with stirring overnight. The mixture was diluted with ether (50 ml) and the solids were isolated by filtration to provide 0.7 g N-(6-aminohexyl)acetamidine as a white solid (66% yield from N-Boc-1,6-diaminohexane). M.P.=163°-164° C. Mass spectrum (CI) 158.1 (MH+, 100%). the solids were isolated by filtration

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: To a solution of 6-(Boc-amino)hexylamine (4.95 g, 23 mmol) and Et3N (2 eq, 6.4 ml, 46 mmol) in 25 ml CH3CN was added dropwise 4-phenoxybenzenesulfonyl chloride solution (1 eq, 6.16 g, 23 mmol) in 15 ml CH3CN. The reaction was stirred for 2 days at room temperature. The precipitate was filtered and the solvent was evaporated. The residue was purified by silica gel chromatography [eluent: CH2Cl2/1-2% MeOH] to yield 6.68 g (64%) a colorless oil, which solidified to a white solid, m.p.=77-78° C. The precipitate was filtered the solvent was evaporated The residue was purified by silica gel chromatography [eluent: CH2Cl2/1-2% MeOH]

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

実験手順: To a solution of 6-(Boc-amino)hexylamine (4.95 g, 23 mmol) and Et3N (2 eq, 6.4 ml, 46 mmol) in 25 ml CH3CN was added dropwise 4-phenoxybenzenesulfonyl chloride solution (1 eq, 6.16 g, 23 mmol) in 15 ml CH3CN. The reaction was stirred for 2 days at room temperature. The precipitate was filtered and the solvent was evaporated. The residue was purified by silica gel chromatography [eluent: CH2Cl2/1-2% MeOH] to yield 6.68 g (64%) a colorless oil, which solidified to a white solid, m.p.=77-78° C. The precipitate was filtered the solvent was evaporated The residue was purified by silica gel chromatography [eluent: CH2Cl2/1-2% MeOH]

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 6-(8-Methyl-4-oxo-4H-1,3-benzothiazin-2-yl)-2-pyridinecarboxylic acid (1.5 g, 5.0 mmol) was dissolved in DMF (15 ml) and N-(tert-butoxycarbonyl)-1,6-diaminohexane (2.1 g, 10.0 mmol), WSC (3.0 g, 15.5 mmol) and HOBt (2.0 g, 14.9 mmol) were added thereto. The reaction mixture was stirred at 80° C. for 10 hrs and combined with ethyl acetate and water. The organic layer was washed with saturated brine and dried over magnesium sulfate. The solvent was evaporated and the residue was subjected to a silica gel column chromatography. The fractions eluted with ethyl acetate-hexane (4:1, v/v) were collected, concentrated and recrystallized from hexane-tetrahydrofuran to give the titled compound (1.1 g, 45%) as white crystals. The organic layer was washed with saturated brine dried over magnesium sulfate The solvent was evaporated The fractions eluted with ethyl acetate-hexane (4:1 v/v) were collected concentrated recrystallized from hexane-tetrahydrofuran

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 6-(8-Methyl-4-oxo-4H-1,3-benzothiazin-2-yl)-2-pyridinecarboxylic acid (1.5 g, 5.0 mmol) was dissolved in DMF (15 ml) and N-(tert-butoxycarbonyl)-1,6-diaminohexane (2.1 g, 10.0 mmol), WSC (3.0 g, 15.5 mmol) and HOBt (2.0 g, 14.9 mmol) were added thereto. The reaction mixture was stirred at 80° C. for 10 hrs and combined with ethyl acetate and water. The organic layer was washed with saturated brine and dried over magnesium sulfate. The solvent was evaporated and the residue was subjected to a silica gel column chromatography. The fractions eluted with ethyl acetate-hexane (4:1, v/v) were collected, concentrated and recrystallized from hexane-tetrahydrofuran to give the titled compound (1.1 g, 45%) as white crystals. The organic layer was washed with saturated brine dried over magnesium sulfate The solvent was evaporated The fractions eluted with ethyl acetate-hexane (4:1 v/v) were collected concentrated recrystallized from hexane-tetrahydrofuran

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

実験手順: The reaction was carried out in the same manner as in Example 7 except for using 9.06 g (69.6 mmole) of 5-fluorouracil, 6.20 g (62.7 mmole) of phosgene, 12.68 g (125.3 mmole) of triethylamine, and 11.36 g (52.5 mmole) of N-(t-butyoxycarbonyl)hexamethylenediamine synthesized in Reference example 13 in place of N-[N-(2-n-propyl-n-pentanoyl)-glycyl]hexamethylenediamine used in Example 7. The reaction mixture was treated in the same manner as in Example 7 to give 16.06 g (Yield: 91.3%) of pale yellowish crystals. 1 g of this crystals was recrystallized from 15 ml of ethyl acetate to give 0.52 g of colorless needle crystals. The reaction mixture was treated in the same manner as in Example 7

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

実験手順: The reaction was carried out in the same manner as in Example 7 except for using 9.06 g (69.6 mmole) of 5-fluorouracil, 6.20 g (62.7 mmole) of phosgene, 12.68 g (125.3 mmole) of triethylamine, and 11.36 g (52.5 mmole) of N-(t-butyoxycarbonyl)hexamethylenediamine synthesized in Reference example 13 in place of N-[N-(2-n-propyl-n-pentanoyl)-glycyl]hexamethylenediamine used in Example 7. The reaction mixture was treated in the same manner as in Example 7 to give 16.06 g (Yield: 91.3%) of pale yellowish crystals. 1 g of this crystals was recrystallized from 15 ml of ethyl acetate to give 0.52 g of colorless needle crystals. The reaction mixture was treated in the same manner as in Example 7