1-N,1-N-diethylpropane-1,2-diamine

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

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

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

Procedure: To a stirred solution of 4-(iso-butyryl-N-methylamino)-benzoic acid (0.088 g) and triethylamine (0.041 g) in chloroform (4 ml) was added a solution of ethyl chlorformate (0.049 g) in chloroform (1 ml). The mixture was stirred under an N2 atmosphere at room temperature for 1½ hours and then cooled to 0° C. N,N-Diethyl-propylenediamine (0.051 g) in chloroform (1 ml) was added and the mixture was stirred over night. The mixture were washed with 0.5 M NaOH(aq) and water. Drying and evaporation of the solvent gave a residue, which was chromatographed on a silica gel column first eluted/washed with ethylacetate and then eluted with ethylacetate-methanol-triethylamine (12:4:1) to yield 0.098 g, of the title product. cooled to 0° C the mixture was stirred over night The mixture were washed with 0.5 M NaOH(aq) and water Drying evaporation of the solvent gave a residue, which was chromatographed on a silica gel column first eluted/washed with ethylacetate eluted with ethylacetate-methanol-triethylamine (12:4:1) to yield 0.098 g

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

Procedure: A mixture of 12.15 g (0.075 mole) of 1,1'-carbonyl diimidazole and 7.50 g (0.0476 mole) of 1-diethylamino-2-propanamine in 400 ml of tetrahydrofuran was stirred at room temperature for 1 hr. A solution of 12.26 g (0.054 mole) of N-[2-(phenylsulfonyl)ethyl]-2-propanamine in 50 ml of tetrahydrofuran was added, and the solution was refluxed for 19 hr. The solvent was removed in vacuo, and the residue was dissolved in a 50/50 mixture of methylene chloride and ether. The organic solution was extracted with several portions of water and was dried over magnesium sulfate. The solvent was removed in vacuo to give an oil. Flash chromatography on silica gel (elution with methanol) gave 10.87 g (52.3 g) of clear colorless oil. 1H NMR (CDCl3)δ7.5-8.15 (m, s. aromatic), 5.35 (br s, 1, NH), 4.1 (m, 1, (CH3)2CH), 3.45-4.0 (m, 1. NHCH(CH3)CH2), 2.5-2.85 (m, 6, CH2CH3)), 0.85-1.3 (m, 15, CH3 groups). the solution was refluxed for 19 hr The solvent was removed in vacuo the residue was dissolved in a 50/50 mixture of methylene chloride and ether The organic solution was extracted with several portions of water was dried over magnesium sulfate The solvent was removed in vacuo to give an oil

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

Procedure: 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (51 mg) was then added to the solution, and the mixture was stirred at room temperature for 6 hr. Next, N,N-diethylpropylenediamine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 14 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (25 mg, yield %). the mixture was further stirred at room temperature for 14 hr by washing with water and saturated brine in that order The organic layer was then dried over anhydrous sodium sulfate The solvent was removed by distillation under the reduced pressure the residue was purified by HPLC

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

Procedure: 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (51 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (51 mg) was then added to the solution, and the mixture was stirred at room temperature for 6 hr. Next, N,N-diethylpropylenediamine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 16 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (38 mg, yield 49%). the mixture was further stirred at room temperature for 16 hr by washing with water and saturated brine in that order The organic layer was then dried over anhydrous sodium sulfate The solvent was removed by distillation under the reduced pressure the residue was purified by HPLC

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

Procedure: 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (51 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (51 mg) was then added to the solution, and the mixture was stirred at room temperature for 6 hr. Next, N,N-diethylpropylenediamine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 16 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (38 mg, yield 49%). the mixture was further stirred at room temperature for 16 hr by washing with water and saturated brine in that order The organic layer was then dried over anhydrous sodium sulfate The solvent was removed by distillation under the reduced pressure the residue was purified by HPLC

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

Procedure: 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (51 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (51 mg) was then added to the solution, and the mixture was stirred at room temperature for 6 hr. Next, N,N-diethylpropylenediamine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 15 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (36 mg, yield 45%). the mixture was further stirred at room temperature for 15 hr by washing with water and saturated brine in that order The organic layer was then dried over anhydrous sodium sulfate The solvent was removed by distillation under the reduced pressure the residue was purified by HPLC

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

Procedure: 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (51 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (50 mg) was then added to the solution, and the mixture was stirred at room temperature for 1 hr. Next, N,N-diethylpropylenediamine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 6 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (19 mg, yield 24%). the mixture was further stirred at room temperature for 6 hr by washing with water and saturated brine in that order The organic layer was then dried over anhydrous sodium sulfate The solvent was removed by distillation under the reduced pressure the residue was purified by HPLC

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

Procedure: 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (51 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (50 mg) was then added to the solution, and the mixture was stirred at room temperature for 1 hr. Next, N,N-diethylpropylenediamine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 6 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (19 mg, yield 24%). the mixture was further stirred at room temperature for 6 hr by washing with water and saturated brine in that order The organic layer was then dried over anhydrous sodium sulfate The solvent was removed by distillation under the reduced pressure the residue was purified by HPLC

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

Procedure: 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (50 mg) was then added to the solution, and the mixture was stirred at room temperature for 6 hr. Next, N,N-diethylpropylenediamine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 15 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (10 mg, yield 12%). the mixture was further stirred at room temperature for 15 hr by washing with water and saturated brine in that order The organic layer was then dried over anhydrous sodium sulfate The solvent was removed by distillation under the reduced pressure the residue was purified by HPLC

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

Procedure: 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (50 mg) was then added to the solution, and the mixture was stirred at room temperature for 6 hr. Next, N,N-diethylpropylenediamine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 15 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (10 mg, yield 12%). the mixture was further stirred at room temperature for 15 hr by washing with water and saturated brine in that order The organic layer was then dried over anhydrous sodium sulfate The solvent was removed by distillation under the reduced pressure the residue was purified by HPLC