1-isocyanatotetradecane

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

Procedure: The preparation is analogous to Example 42, starting from 7.0 g of the compound of Example 1 and 4.8 g of tetradecyl isocyanate.

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

Procedure: To a vigorously-stirred, biphasic mixture of 1-tetradecylamine (9.44 g, 44.2 mmol) in CH2Cl2 (300 mL) and potassium bicarbonate (21.8 g, 158 mmol) in H2O (200 mL) was added (dropwise) a 1.93 M solution of phosgene in toluene (30.0 mL, 57.9 mmol) at 0° C. After 30 min, the organic layer was separated and dried over MgSO4. The volatile components were removed with a rotary evaporator to afford crude tetradecyl isocyanate which was immediately taken up in THF (15 mL) and added to a heterogeneous mixture of 5,6-dichlorobenzotriazole (5.94 g, 31.6 mmol) and THF (125 mL). The reaction mixture was stirred at ambient temperature for 14 h, and the volatile components were then removed with a rotary evaporator. The crude product was first purified by silica gel column chromatography (heptane: ethyl acetate=7:3) and then recrystallized from ethanol to afford 12.2 g (90%) of D12. the organic layer was separated dried over MgSO4 The volatile components were removed with a rotary evaporator

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

Procedure: To a vigorously-stirred, biphasic mixture of 1-tetradecylamine (9.44 g, 44.2 mmol) in CH2Cl2 (300 mL) and potassium bicarbonate (21.8 g, 158 mmol) in H2O (200 mL) was added (dropwise) a 1.93 M solution of phosgene in toluene (30.0 mL, 57.9 mmol) at 0° C. After 30 min, the organic layer was separated and dried over MgSO4. The volatile components were removed with a rotary evaporator to afford crude tetradecyl isocyanate which was immediately taken up in THF (15 mL) and added to a heterogeneous mixture of 5,6-dichlorobenzotriazole (5.94 g, 31.6 mmol) and THF (125 mL). The reaction mixture was stirred at ambient temperature for 14 h, and the volatile components were then removed with a rotary evaporator. The crude product was first purified by silica gel column chromatography (heptane: ethyl acetate=7:3) and then recrystallized from ethanol to afford 12.2 g (90%) of D12. the organic layer was separated dried over MgSO4 The volatile components were removed with a rotary evaporator

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

Procedure: Melting point 100° C., with decomposition. IR(CHCl3) 1,562, 1,580, 1,602, 1,618, 1,665 and 1,725 cm-1. ##STR91## The starting material 3-methyl-2,4-dioxo-1,2,3,4-tetrahydro-s-triazino-[1,2-a]-benzimidazole is known from German Published Specification DOS 2,144,505 ##STR92## The starting material 3-phenyl-2,4-dioxo-1,2,3,4-tetrahydro-s-triazino-[1,2-a]-benzimidazole is known from German Published Specification DOS 2,144,505. ##STR93## The starting material 3-tetradecyl-2,4-dioxo-1,2,3,4-tetrahydro-s-triazino-[1,2-a]-benzimidazol (m.p. 193° C.) is obtained by reacting 1 -(benzimidazole-2-yl)-3-tetradecylurea and diphenylcarbonate. 1-(benzimidazole-2-yl)-3-tetradecylurea is formed by the reaction of 2-aminobenzimidazole and tetradecylisocyanate in xylene at 120° C. ##STR94## The starting material 3-cyclohexyl-2,4-dioxo-1,2,3,4-tetrahydro-s-triazino[1,2-a]-benzimidazole (m.p. 335° C.) is obtained from 1-(benzimidazole-2-yl)-3-cyclohexylurea and diphenylcarbonate. 1-(benzimidazole-2-yl)-3-cyclohexylurea is obtained from 2-aminobenzimidazole and cyclohexylisocyanate at about 120° C. in xylene. ##STR95## The starting material 3-(2-phenylethyl)-2,4-dioxo-1,2,3,4-tetrahydro-s-triazino-[1,2-a]-benzimidazole (m.p. 298° C.) is produced from diphenylcarbobate and 1-(benzimidazole-2-yl)-3-(2-phenylethyl)-urea. The latter is produced from N-benzimidazole-2-yl-carbamic acid phenyl ester and 2-phenylethylamine. ##STR96## The starting material 3-(ω-methylamino-carbonylpentyl)-2,4-dioxo-1,2,3,4-tetrahydro-s-triazino-[1,2-a]-benzimidazole (m.p. 268° C. destr.) is formed by boiling 3-(ω-methoxycarbonylpentyl)-2,4-dioxo-1,2,3,4-tetrahydro-s-triazino-[1,2-a]-benzimidazole (m.p. 221° C.) in a mixture of butanol and water with methylamine.

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

Procedure: Melting point 100° C., with decomposition. IR(CHCl3) 1,562, 1,580, 1,602, 1,618, 1,665 and 1,725 cm-1. ##STR91## The starting material 3-methyl-2,4-dioxo-1,2,3,4-tetrahydro-s-triazino-[1,2-a]-benzimidazole is known from German Published Specification DOS 2,144,505 ##STR92## The starting material 3-phenyl-2,4-dioxo-1,2,3,4-tetrahydro-s-triazino-[1,2-a]-benzimidazole is known from German Published Specification DOS 2,144,505. ##STR93## The starting material 3-tetradecyl-2,4-dioxo-1,2,3,4-tetrahydro-s-triazino-[1,2-a]-benzimidazol (m.p. 193° C.) is obtained by reacting 1 -(benzimidazole-2-yl)-3-tetradecylurea and diphenylcarbonate. 1-(benzimidazole-2-yl)-3-tetradecylurea is formed by the reaction of 2-aminobenzimidazole and tetradecylisocyanate in xylene at 120° C. ##STR94## The starting material 3-cyclohexyl-2,4-dioxo-1,2,3,4-tetrahydro-s-triazino[1,2-a]-benzimidazole (m.p. 335° C.) is obtained from 1-(benzimidazole-2-yl)-3-cyclohexylurea and diphenylcarbonate. 1-(benzimidazole-2-yl)-3-cyclohexylurea is obtained from 2-aminobenzimidazole and cyclohexylisocyanate at about 120° C. in xylene. ##STR95## The starting material 3-(2-phenylethyl)-2,4-dioxo-1,2,3,4-tetrahydro-s-triazino-[1,2-a]-benzimidazole (m.p. 298° C.) is produced from diphenylcarbobate and 1-(benzimidazole-2-yl)-3-(2-phenylethyl)-urea. The latter is produced from N-benzimidazole-2-yl-carbamic acid phenyl ester and 2-phenylethylamine. ##STR96## The starting material 3-(ω-methylamino-carbonylpentyl)-2,4-dioxo-1,2,3,4-tetrahydro-s-triazino-[1,2-a]-benzimidazole (m.p. 268° C. destr.) is formed by boiling 3-(ω-methoxycarbonylpentyl)-2,4-dioxo-1,2,3,4-tetrahydro-s-triazino-[1,2-a]-benzimidazole (m.p. 221° C.) in a mixture of butanol and water with methylamine.

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

Procedure: To a vigorously-stirred, biphasic mixture of 1-tetradecylamine (9.44 g, 44.2 mmol) in CH2Cl2 (300 mL) and potassium bicarbonate (21.8 g, 158 mmol) in H2O (200 mL) was added (dropwise) a 1.93 M solution of phosgene in toluene (30.0 mL, 57.9 mmol) at 0° C. After 30 min, the organic layer was separated and dried over MgSO4. The volatile components were removed with a rotary evaporator to afford crude tetradecyl isocyanate which was immediately taken up in THF (15 mL) and added to a heterogeneous mixture of 5,6-dichlorobenzotriazole (5.94 g, 31.6 mmol) and THF (125 mL). The reaction mixture was stirred at ambient temperature for 14 h, and the volatile components were then removed with a rotary evaporator. The crude product was first purified by silica gel column chromatography (heptane:ethyl acetate=7:3) and then recrystallized from ethanol to afford 12.2 g (90%) of D12. the organic layer was separated dried over MgSO4 The volatile components were removed with a rotary evaporator

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

Procedure: To a vigorously-stirred, biphasic mixture of 1-tetradecylamine (9.44 g, 44.2 mmol) in CH2Cl2 (300 mL) and potassium bicarbonate (21.8 g, 158 mmol) in H2O (200 mL) was added (dropwise) a 1.93 M solution of phosgene in toluene (30.0 mL, 57.9 mmol) at 0° C. After 30 min, the organic layer was separated and dried over MgSO4. The volatile components were removed with a rotary evaporator to afford crude tetradecyl isocyanate which was immediately taken up in THF (15 mL) and added to a heterogeneous mixture of 5,6-dichlorobenzotriazole (5.94 g, 31.6 mmol) and THF (125 mL). The reaction mixture was stirred at ambient temperature for 14 h, and the volatile components were then removed with a rotary evaporator. The crude product was first purified by silica gel column chromatography (heptane:ethyl acetate=7:3) and then recrystallized from ethanol to afford 12.2 g (90%) of D12. the organic layer was separated dried over MgSO4 The volatile components were removed with a rotary evaporator

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

Procedure: To a vigorously-stirred, biphasic mixture of 1-tetradecylamine (9.44 g, 44.2 mmol) in CH2Cl2 (300 mL) and potassium bicarbonate (21.8 g, 158 mmol) in H2O (200 mL) was added (dropwise) a 1.93 M solution of phosgene in toluene (30.0 mL, 57.9 mmol) at 0° C. After 30 min, the organic layer was separated and dried over MgSO4. The volatile components were removed with a rotary evaporator to afford crude tetradecyl isocyanate which was immediately taken up in THF (15 mL) and added to a heterogeneous mixture of 5,6-dichlorobenzotriazole (5.94 g, 31.6 mmol) and THF (125 mL). The reaction mixture was stirred at ambient temperature for 14 h, and the volatile components were then removed with a rotary evaporator. The crude product was first purified by silica gel column chromatography (heptane:ethyl acetate=7:3) and then recrystallized from ethanol to afford 12.2 g (90%) of D12. the organic layer was separated dried over MgSO4 The volatile components were removed with a rotary evaporator

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

Procedure: (5.1) To a stirring solution of 5-amino-3-methyl-thiophene-2,4-dicarboxylic acid 2-octyl ester 4-tert-butyl ester (348 mg, 0.94 mmol) and DBU (0.35 mL, 360 mg, 2.4 mmol) in CH2Cl2 (10 mL) was added octyl isocyanate (0.166 mL, 146 mg, 0.94 mmol). The reaction was stirred RT for 16 h, and then solvent was removed under reduced pressure. The product was purified by column chromatography (5:1; hexanes:EtOAc) to give 431 mg of a solid (87%): Mp 92.0-94.0° C.; 1H NMR (CDCl3) δ 12.30 (s, 1H), 8.64 (s, 1H), 5.30 (t, 1H, J=6.0 Hz), 4.25 (t, 2H, J=6.4 Hz), 3.29 (q, 2H, J=6.0 Hz), 2.74 (s, 3H), 1.90-1.50 (m, 4H), 1.61 (s, 9H), 1.28 (bs, 20H), 0.88 (m, 6H). MS (EI): 525.1 (m+). 3-Methyl-5-(3-octyl-ureido)-thiophene-2,4-dicarboxylic acid 2-benzyl ester 4-tert-butyl ester. (5.2) The same method as for the preparation of 3-methyl-5-(3-octyl-ureido)-thiophene-2,4-dicarboxylic acid 4-tert-butyl ester 2-octyl ester was employed. Thus, acylation with octyl isocyanate (3.83 mL, 3.37 g, 21.7 mmol) afforded 3.42 g of a solid (38%) after column chromatography (9:1; hexanes:EtOAc): Mp 119.0-120.0° C.; 1H NMR (CDCl3) δ 11.03 (s, 1H), 7.50-7.20 (m, 5H), 5.27 (s, 2H), 5.03 (vt, 1H), 3.29 (q, 2H, J=6.6 Hz), 2.71 (s, 3H), 1.63-1.40 (m, 2H), 1.57 (s, 9H), 1.26 (bs, 10H), 0.87 (t, 3H, J=6.6 Hz). MS (EI): 502.8 (m+). 3-Methyl-5-(3-tetradecyl-ureido)-thiophene-2,4-dicarboxylic acid 2-benzyl ester 4-tert-butyl ester. (5.3) The same method as for the preparation of 3-methyl-5-(3-octyl-ureido)-thiophene-2,4-dicarboxylic acid 4-tert-butyl ester 2-octyl ester was employed. Thus, acylation with tetradecyl isocyanate (0.33 mL, 287 mg, 1.2 mmol) afforded 253 mg of a solid (36%) after column chromatography (9:1; hexanes:EtOAc): Mp 104.5-106.0° C.; 1H NMR (CDCl3) δ 11.04 (s, 1H), 7.50-7.20 (m, 5H), 5.27 (s, 2H), 5.14 (t, 1H, J=6.2 Hz), 3.29 (q, 2H, J=6.2 Hz), 2.71 (s, 3H), 1.65-1.40 (m, 2H), 1.57 (s, 9H), 1.25 (bs, 22H), 0.88 (t, 3H, J=6.0 Hz). MS (EI): 587.1 (m+). 5-(3-Hexadecyl-ureido)-3-methyl-thiophene-2,4-dicarboxylic acid 2-benzyl ester 4-tert-butyl ester. (5.4) The same method as for the preparation of 3-methyl-5-(3-octyl-ureido)-thiophene-2,4-dicarboxylic acid 4-tert-butyl ester 2-octyl ester was employed. Thus, acylation with hexadecyl isocyanate (0.37 mL, 321 mg, 1.2 mmol) afforded 218 mg of a solid (30%) after column chromatography (9:1; hexanes:EtOAc): Mp 104.0-105.0° C.; 1H NMR (CDCl3) δ 11.04 (s, 1H), 7.50-7.20 (m, 5H), 5.27 (s, 2H), 5.14 (t, 1H, J=6.2 Hz), 3.29 (q, 2H, J=6.2 Hz), 2.71 (s, 3H), 1.65-1.40 (m, 2H), 1.57 (s, 9H), 1.25 (bs, 26H), 0.88 (t, 3H, J=6.0 Hz). MS (EI): 615.1 (m+). 5-(3-Dodecyl-ureido)-3-methyl-thiophene-2,4-dicarboxylic acid 2-benzyl ester 4-tert-butyl ester. (5.5) The same method as for the preparation of 3-methyl-5-(3-octyl-ureido)-thiophene-2,4-dicarboxylic acid 4-tert-butyl ester 2-octyl ester was employed. Thus, acylation with decyl isocyanate (0.29 mL, 254 mg, 1.2 mmol) afforded 265 mg of a solid (40%) after column chromatography (9:1; hexanes:EtOAc): Mp 106.8-108.0° C.). 1H NMR (CDCl3) δ 11.04 (s, 1H), 7.45-7.26 (m, 5H), 5.27 (s, 2H), 5.24 (t, 1H, J=5.6 Hz), 3.28 (q, 2H, J=6.6 Hz), 2.72 (s, 3H), 1.60-1.40 (m, 2H), 1.57 (s, 9H), 1.25 (bs, 18H), 0.88 (t, 3H, J=6.4 Hz). MS (EI): 559.0 (m+).

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

Procedure: Using this procedure, the reaction of 4-nitrocatechol with tetradecyl isocyanate gave 3,4-bis [[(tetradecylamino)carbonyl]oxy]nitrobenzene (mp 100°-104°). The structure was confirmed by the nmr spectrum.

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

Procedure: Triethylamine (1.06 ml) and tetradecyl isocyanate (1.64 g) were added to a solution containing 3-(2-hydroxyphenyl)-1-(4-methylpiperazino)-1-propanone (1.70 g) obtained in Example 3(1) in methylene chloride (17 ml). After being stirred for 18.5 hours at room temperature, the reaction mixture was diluted with chloroform, washed with saturated sodium hydrogencarbonate aqueous solution and brine successively, dried over sodium sulfate anhydride, and concentrated. The residue was purified by silica gel column chromatography (silica gel 100 g, chloroform:methanol=60:1 to 30:1), thereby yielding the entitled compound (3.04 g) as white solid. washed with saturated sodium hydrogencarbonate aqueous solution and brine successively dried over sodium sulfate anhydride concentrated The residue was purified by silica gel column chromatography (silica gel 100 g, chloroform:methanol=60:1 to 30:1)

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

Procedure: Triethylamine (1.06 ml) and tetradecyl isocyanate (1.64 g) were added to a solution containing 3-(2-hydroxyphenyl)-1-(4-methylpiperazino)-1-propanone (1.70 g) obtained in Example 3(4) in methylene chloride (17 ml). After being stirred for 18.5 hours at room temperature, the reaction mixture was diluted with chloroform, washed with saturated sodium hydrogencarbonate aqueous solution and brine successively, dried over sodium sulfate anhydride, and concentrated. The residue was purified by silica gel column chromatography (silica gel 100 g, chloroform:methanol=60:1 to 30:1), thereby yielding the entitled compound (3.04 g) as white solid. washed with saturated sodium hydrogencarbonate aqueous solution and brine successively dried over sodium sulfate anhydride concentrated The residue was purified by silica gel column chromatography (silica gel 100 g, chloroform:methanol=60:1 to 30:1)