N-propylbenzamide

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 32.6 g of isatoic anhydride in 150 ml of isopropyl alcohol was added 25 ml of n-propylamine portionwise as the reaction was exothermic. Evaporation of the solution gave 30 g of 2-amino-N-propylbenzamide as colorless crystals, mp 100°-102° C. To a stirred solution of 25.0 g of 2-amino-N-propylbenzamide in 300 ml of tetrahydrofuran was added 22.9 g of benzoylisothiocyanate over 10 minutes. After 2 hours the mixture was diluted with 100 ml of ether and was filtered to give 30.7 g of 2-[[benzoylamino)thioxomethyl]amino]-N-propylbenzamide, mp 172°-174° C. Then, to a solution of 10.2 g of 2-[[benzoylamino)thioxomethyl]amino]-N-propylbenzamide in 100 ml of dichloromethane was added 30 ml of 1N sodium hydroxide to form a two-phase mixture, and to this was added 20 ml of iodomethane and then 4 drops of benzyltrimethylammonium hydroxide solution. After stirring for 3 hours, the organic phase was separated and dried over anhydrous sodium sulfate. Filtration and evaporation of the filtrate gave 9.4 g of N-benzoyl-N'-(2-propylaminocarbonylphenyl)carbamimidothioic acid, methyl ester, mp 86°-89° C. To a solution of 7.10 g of this compound in 300 ml of anhydrous dioxane was added 1.45 g of 60% sodium hydride in mineral oil suspension and the mixture was refluxed for 5 hours. The reaction mixture was then poured into 1.5 liter of water and made acidic with hydrochloric acid. The crystals that formed were collected and recrystallized from ethyl acetate-hexane to give N-(3,4-dihydro-3-propyl-4oxo-2-quinazolinyl)benzamide as colorless crystals, mp 133°-135° C. was filtered

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

Procedure: (5RS,6SR,7SR)-6-Tert-butoxycarbonyl-7-(2-benzyloxy-4-methoxyphenyl)-5-(3,4-methylenedioxyphenyl)cyclopenteno[1,2-b]pyridine N-oxide(224 mg, 0.395 mmol) and CsF(1.82 g) were dried under reduced pressure. To the mixture were added dichloromethane(4.0 ml) under nitrogen atmosphere and N-propylbenzimidoyl chloride(210 mg) which was prepared from benzoic acid N-propylamide and thionyl chloride. The solution was stirred vigorously under heating at reflux, treated with an aqueous saturated solution of NaHCO3 and water, stirred at room temperature to make the solution homogeneous and extracted with dichloromethane. The organic layer was washed with brine and dried over MgSO4. After removal of the solvent the residue was purified by MPL(E. Merck Kieselgel 60 lobar column/dichloromethane:acetone=100:1 to 50:1 to 30:1) to give (5RS,6SR,7SR)-6-tert-butoxycarbonyl-7-(2-benzyloxy-4-methoxyphenyl)-2-[(N-benzoyl)propylamino]-5-(3,4-methylenedioxyphenyl)cyclopenteno[1,2-b]pyridine(138 mg). under heating at reflux stirred at room temperature extracted with dichloromethane The organic layer was washed with brine dried over MgSO4 After removal of the solvent the residue was purified by MPL(E

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

Procedure: (5RS,6SR,7SR)-6-Tert-butoxycarbonyl-7-(2-benzyloxy-4-methoxyphenyl)-5-(3,4-methylenedioxyphenyl)cyclopenteno[1,2-b]pyridine N-oxide(224 mg, 0.395 mmol) and CsF(1.82 g) were dried under reduced pressure. To the mixture were added dichloromethane(4.0 ml) under nitrogen atmosphere and N-propylbenzimidoyl chloride(210 mg) which was prepared from benzoic acid N-propylamide and thionyl chloride. The solution was stirred vigorously under heating at reflux, treated with an aqueous saturated solution of NaHCO3 and water, stirred at room temperature to make the solution homogeneous and extracted with dichloromethane. The organic layer was washed with brine and dried over MgSO4. After removal of the solvent the residue was purified by MPL(E. Merck Kieselgel 60 lobar column/dichloromethane:acetone=100:1 to 50:1 to 30:1) to give (5RS,6SR,7SR)-6-tert-butoxycarbonyl-7-(2-benzyloxy-4-methoxyphenyl)-2-[(N-benzoyl)propylamino]-5-(3,4-methylenedioxyphenyl)cyclopenteno[1,2-b]pyridine(138 mg). under heating at reflux stirred at room temperature extracted with dichloromethane The organic layer was washed with brine dried over MgSO4 After removal of the solvent the residue was purified by MPL(E

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: A solution of benzoyl chloride (116 μL, 1 mmol) in 1 mL of dry CH2Cl2 was treated successively at 0° C. with triethylamine (167 μL, 1.2 mmol) and n-propylamine (124 μL, 1.5 mmol). The reaction was stirred at room temperature for two hours. The resulting reaction mixture was diluted with CH2Cl2 washed with 2M HCl, followed by saturated NaHCO3, then brine. The resulting solution was then dried over MgSO4. The residue was purified using SiO2 with CH2Cl2/Petroluem ether 95:5 to CH2Cl2 100%. A white solid was obtained (166 mg, quantitative yield). NMR 1H (ppm, CDCl3): 7.74 (d, J3=8.1 Hz, 2H), 7.41 (t. t., J3=7.2 Hz, J4=1.3 Hz, 1H), 7.33 (t. t., J3=7.6 Hz, J4=1.6 Hz, 2H), 5.23 (br. s., 1H), 3.36-3.30 (m, 2H), 1.57 (sext., J3=7.2 Hz, 2H), 0.90 (t, J3=7.4 Hz, 3H). The resulting reaction mixture washed with 2M HCl The resulting solution was then dried over MgSO4 The residue was purified A white solid was obtained (166 mg, quantitative yield)

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

Procedure: A solution of benzoyl chloride (116 μL, 1 mmol) in 1 mL of dry CH2Cl2 was treated successively at 0° C. with triethylamine (167 μL, 1.2 mmol) and n-propylamine (124 μL, 1.5 mmol). The reaction was stirred at room temperature for two hours. The resulting reaction mixture was diluted with CH2Cl2 washed with 2M HCl, followed by saturated NaHCO3, then brine. The resulting solution was then dried over MgSO4. The residue was purified using SiO2 with CH2Cl2/Petroluem ether 95:5 to CH2Cl2 100%. A white solid was obtained (166 mg, quantitative yield). NMR 1H (ppm, CDCl3): 7.74 (d, J3=8.1 Hz, 2H), 7.41 (t. t., J3=7.2 Hz, J4=1.3 Hz, 1H), 7.33 (t. t., J3=7.6 Hz, J4=1.6 Hz, 2H), 5.23 (br. s., 1H), 3.36-3.30 (m, 2H), 1.57 (sext., J3=7.2 Hz, 2H), 0.90 (t, J3=7.4 Hz, 3H). The resulting reaction mixture washed with 2M HCl The resulting solution was then dried over MgSO4 The residue was purified A white solid was obtained (166 mg, quantitative yield)

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

Procedure: A solution of benzoyl chloride (116 μL, 1 mmol) in 1 mL of dry CH2Cl2 was treated successively at 0° C. with triethylamine (167 μL, 1.2 mmol) and n-propylamine (124 μL, 1.5 mmol). The reaction was stirred at room temperature for two hours. The resulting reaction mixture was diluted with CH2Cl2 washed with 2M HCl, followed by saturated NaHCO3, then brine. The resulting solution was then dried over MgSO4. The residue was purified using SiO2 with CH2Cl2/Petroluem ether 95:5 to CH2Cl2 100%. A white solid was obtained (166 mg, quantitative yield). NMR 1H (ppm, CDCl3): 7.74 (d, J3=8.1 Hz, 2H), 7.41 (t. t., J3=7.2 Hz, J4=1.3 Hz, 1H), 7.33 (t. t., J3=7.6 Hz, J4=1.6 Hz, 2H), 5.23 (br. s., 1H), 3.36-3.30 (m, 2H), 1.57 (sext., J3=7.2 Hz, 2H), 0.90 (t, J3=7.4 Hz, 3H). The resulting reaction mixture washed with 2M HCl The resulting solution was then dried over MgSO4 The residue was purified A white solid was obtained (166 mg, quantitative yield)

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

Procedure: Dry DCM (30 mL) was added to benzoyl chloride (2.06 mL, 17.7 mmol) followed by the dropwise addition of propylamine (3.19 mL, 38.9 mmol) over 5 min at 0° C. The system was stirred at 0° C. under nitrogen for 1 h and monitored by TLC. After 1 h the system was washed with 1M HCl (20 mL), brine (10 mL) and dried with MgSO4. The solvent was removed to give N-Propylbenzamide as a white solid (2.6 g, 15.9 mmol, 90%); Rf 0.38 (40:60 EtOAc:petrol). mp 87.6-88.9° C. Lit. 83-84° C.7 1H NMR: (300 MHz, CDCl3) δ 0.90 (t, 3H, J=7.4 Hz, CH2—CH2—CH3), 1.56 (sex, 2H, J=7.2 Hz, N—CH2—CH2), 3.33 (m, 2H, N—CH2), 6.21 (bs, 1H, NH), 7.31-7.43 (m, 3H, Ar—H), 7.69 (m, 2H, Ar—H). 13C NMR: (75 MHz, CDCl3) δ 11.8, 23.3, 42.1, 127.2, 128.8, 131.6, 135.2, 167.9. LC/MS-ES+ m/z 164.2 [MH+], 327.1, 328.1. After 1 h the system was washed with 1M HCl (20 mL), brine (10 mL) dried with MgSO4 The solvent was removed

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

Procedure: Dry DCM (30 mL) was added to benzoyl chloride (2.06 mL, 17.7 mmol) followed by the dropwise addition of propylamine (3.19 mL, 38.9 mmol) over 5 min at 0° C. The system was stirred at 0° C. under nitrogen for 1 h and monitored by TLC. After 1 h the system was washed with 1M HCl (20 mL), brine (10 mL) and dried with MgSO4. The solvent was removed to give N-Propylbenzamide as a white solid (2.6 g, 15.9 mmol, 90%); Rf 0.38 (40:60 EtOAc:petrol). mp 87.6-88.9° C. Lit. 83-84° C.7 1H NMR: (300 MHz, CDCl3) δ 0.90 (t, 3H, J=7.4 Hz, CH2—CH2—CH3), 1.56 (sex, 2H, J=7.2 Hz, N—CH2—CH2), 3.33 (m, 2H, N—CH2), 6.21 (bs, 1H, NH), 7.31-7.43 (m, 3H, Ar—H), 7.69 (m, 2H, Ar—H). 13C NMR: (75 MHz, CDCl3) δ 11.8, 23.3, 42.1, 127.2, 128.8, 131.6, 135.2, 167.9. LC/MS-ES+ m/z 164.2 [MH+], 327.1, 328.1. After 1 h the system was washed with 1M HCl (20 mL), brine (10 mL) dried with MgSO4 The solvent was removed