3-isocyanatopropylbenzene

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 188 μL (1.2 mmol, 1.5 eq) 3-phenylpropyl isocyanate are added to a solution of 230 mg (0.81 mmol, 1 eq) of ethyl 3-(3′-methylaminobiphenyl-4-yl)propanoate (prepared in Example 7c) in 10 mL of an 8/2 dichloromethane/triethylamine mixture. The reaction medium is stirred at 40° C. for 12 hours and then hydrolyzed with water and extracted with ethyl acetate. The organic phases are combined, washed with sodium chloride solution and dried over sodium sulfate. The solvents are evaporated off and the residual oil is chromatographed on silica (7/3 heptane/ethyl acetate). 348 mg of ethyl 3-{3′-[1-methyl-3-(3-phenylpropyl)ureido]biphenyl-4-yl}propanoate are obtained in solid form. Yield=96% hydrolyzed with water and extracted with ethyl acetate washed with sodium chloride solution dried over sodium sulfate The solvents are evaporated off the residual oil is chromatographed on silica (7/3 heptane/ethyl acetate)

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 188 μL (1.2 mmol, 1.5 eq) 3-phenylpropyl isocyanate are added to a solution of 230 mg (0.81 mmol, 1 eq) of ethyl 3-(3′-methylaminobiphenyl-4-yl)propanoate (prepared in Example 7c) in 10 mL of an 8/2 dichloromethane/triethylamine mixture. The reaction medium is stirred at 40° C. for 12 hours and then hydrolyzed with water and extracted with ethyl acetate. The organic phases are combined, washed with sodium chloride solution and dried over sodium sulfate. The solvents are evaporated off and the residual oil is chromatographed on silica (7/3 heptane/ethyl acetate). 348 mg of ethyl 3-{3′-[1-methyl-3-(3-phenylpropyl)ureido]biphenyl-4-yl}propanoate are obtained in solid form. Yield=96% hydrolyzed with water and extracted with ethyl acetate washed with sodium chloride solution dried over sodium sulfate The solvents are evaporated off the residual oil is chromatographed on silica (7/3 heptane/ethyl acetate)

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

Procedure: To a solution of 2,2-dimethoxy-2-(4-pyridyl)-1-(4-fluorophenyl)ethanamine (1.22 g, 4.4 mmol) in THF (10 mL) was added a solution of (3-isocyanatopropyl)-benzene (1.61 g, 10 mmol) in THF (10 mL). The resulting mixture was stirred at room temperature for 30 minutes. The reaction was quenched by addition of water (50 mL) and extracted with ethyl acetate (2×50 mL). The combined ethyl acetate extract was washed with water (50 mL), brine (50 mL) and dried with Na2SO4. After removal of solvent, the crude product was purified by column chromatography to yield the product as a light brown solid. The reaction was quenched by addition of water (50 mL) extracted with ethyl acetate (2×50 mL) The combined ethyl acetate extract was washed with water (50 mL), brine (50 mL) dried with Na2SO4 After removal of solvent the crude product was purified by column chromatography

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3-phenylpropyl isocyanate (1.8 mmol) in anhydrous THF (10 mL) at 0° C. under an argon atmosphere was added 2-aminomethyl-pyridine (1.8 mmol). The reaction mixture was stirred at 0° C. for 10 min, the solvent was evaporated under reduced pressure, and the resultant solid was recrystallized from CH2Cl2/Et2O to give pure 59.1 in 92% yield. White solid. m p 89-90° C. When anhydrous benzene was used as solvent the product was directly crystallized out and isolated by filtration (93% yield). the solvent was evaporated under reduced pressure the resultant solid was recrystallized from CH2Cl2/Et2O to give pure 59.1 in 92% yield m p 89-90° C was directly crystallized out isolated by filtration (93% yield)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3-phenylpropyl isocyanate (1.8 mmol) in anhydrous THF (10 mL) at 0° C. under an argon atmosphere was added 2-aminomethyl-pyridine (1.8 mmol). The reaction mixture was stirred at 0° C. for 10 min, the solvent was evaporated under reduced pressure, and the resultant solid was recrystallized from CH2Cl2/Et2O to give pure 59.1 in 92% yield. White solid. m p 89-90° C. When anhydrous benzene was used as solvent the product was directly crystallized out and isolated by filtration (93% yield). the solvent was evaporated under reduced pressure the resultant solid was recrystallized from CH2Cl2/Et2O to give pure 59.1 in 92% yield m p 89-90° C was directly crystallized out isolated by filtration (93% yield)

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 188 μL (1.2 mmol, 1.5 eq) 3-phenylpropyl isocyanate are added to a solution of 230 mg (0.81 mmol, 1 eq) of ethyl 3-(3′-methylaminobiphenyl-4-yl)propanoate (prepared in Example 7c) in 10 mL of an 8/2 dichloromethane/triethylamine mixture. The reaction medium is stirred at 40° C. for 12 hours and then hydrolyzed with water and extracted with ethyl acetate. The organic phases are combined, washed with sodium chloride solution and dried over sodium sulfate. The solvents are evaporated off and the residual oil is chromatographed on silica (7/3 heptane/ethyl acetate). 348 mg of ethyl 3-{3′-[1-methyl-3-(3-phenylpropyl)ureido]biphenyl-4-yl}propanoate are obtained in solid form. Yield=96% hydrolyzed with water and extracted with ethyl acetate washed with sodium chloride solution dried over sodium sulfate The solvents are evaporated off the residual oil is chromatographed on silica (7/3 heptane/ethyl acetate)

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

Procedure: In analogy to the experimental procedure of example 8) 1,6-diaza-spiro[3.3]heptane-1-carboxylic acid tert-butyl ester instead of 1-benzyl-1,6-diaza-spiro[3.3]heptane was converted using (3-isocyanato-propyl)-benzene into the title compound which was used directly in the next step without further purification.

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

Procedure: In analogy to the experimental procedure of example 8) 1,6-diaza-spiro[3.3]heptane-1-carboxylic acid tert-butyl ester instead of 1-benzyl-1,6-diaza-spiro[3.3]heptane was converted using (3-isocyanato-propyl)-benzene into the title compound which was used directly in the next step without further purification.

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

Procedure: To a solution of 1-benzyl-1,6-diaza-spiro[3.3]heptane (41 mg, 217 μmol) in dichloromethane (2 mL) was added diisopropyl-ethyl-amine (112 mg, 868 μmol)) followed by (3-isocyanato-propyl)-benzene (84 mg, 521 μmol) and the reaction mixture was allowed to stir at ambient temperature for 16 h. After complete consumption of starting material the reaction mixture was diluted with dichloromethane and was washed successively with water and brine. The organic layer was dried over sodium sulfate and evaporated under reduced pressure. Purification by HPLC afforded the title compound (9 mg, 12%) as an off-white solid. MS m/e: 350 (M+H)+. After complete consumption of starting material the reaction mixture was diluted with dichloromethane was washed successively with water and brine The organic layer was dried over sodium sulfate evaporated under reduced pressure Purification by HPLC

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

Procedure: In analogy to the experimental procedure of example 8) 1,6-diaza-spiro[3.3]heptane-1-carboxylic acid tert-butyl ester instead of 1-benzyl-1,6-diaza-spiro[3.3]heptane was converted using (3-isocyanato-propyl)-benzene into the title compound which was used directly in the next step without further purification.

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

Procedure: To a solution of 1-benzyl-1,6-diaza-spiro[3.3]heptane (41 mg, 217 μmol) in dichloromethane (2 mL) was added diisopropyl-ethyl-amine (112 mg, 868 μmol)) followed by (3-isocyanato-propyl)-benzene (84 mg, 521 μmol) and the reaction mixture was allowed to stir at ambient temperature for 16 h. After complete consumption of starting material the reaction mixture was diluted with dichloromethane and was washed successively with water and brine. The organic layer was dried over sodium sulfate and evaporated under reduced pressure. Purification by HPLC afforded the title compound (9 mg, 12%) as an off-white solid. MS m/e: 350 (M+H)+. After complete consumption of starting material the reaction mixture was diluted with dichloromethane was washed successively with water and brine The organic layer was dried over sodium sulfate evaporated under reduced pressure Purification by HPLC