6-fluoro-2,3-dihydro-1H-inden-1-amine

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

Procedure: The product of Example 135A and Raney/nickel were processed according to the method of Example 131C to provide the product. MS (ESI+) m/z 152 (M+H)+; to provide the product

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

Procedure: The product of Example 135A and Raney/nickel were processed according to the method of Example 131C to provide the product. MS (ESI+) m/z 152 (M+H)+; to provide the product

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

Procedure: The product of Example 135A and Raney/nickel were processed according to the method of Example 131C to provide the product. MS (ESI+) m/z 152 (M+H)+; to provide the product

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

Procedure: IPEA (0.58 mL), EDC (0.38 g) and HOBT (0.27 g) were added to a suspension of (E)-5-chloro-2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)valeric acid trifluoroacetate (300 mg) and 6-fluoroindan-1-ylamine (CAS #168902-77-0, 151 mg) in DMF (10 mL) at room temperature, and the reaction solution was stirred at room temperature for 12 hours. A saturated aqueous solution of sodium bicarbonate and ethyl acetate were added to the reaction solution and the organic layer was partitioned. The organic layer was washed sequentially with a saturated aqueous solution of ammonium chloride, water and a saturated aqueous solution of sodium chloride. The organic layer was dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (Carrier: Chromatorex™ NH, elution solvent: heptane-ethyl acetate system) to obtain (E)-5-chloro-2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)valeric acid (6-fluoroindan-1-yl)amide (270 mg). Sodium hydride (containing mineral oil at 40%, 60 mg) was added to a solution of (E)-5-chloro-2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)valeric acid (6-fluoroindan-1-yl)amide (270 mg) in DMF (5 mL) at room temperature, and the reaction solution was stirred at room temperature for 30 minutes. A saturated aqueous solution of sodium bicarbonate and ethyl acetate were added to the reaction solution and the organic layer was partitioned. The organic layer was washed sequentially with a saturated aqueous solution of ammonium chloride, water and a saturated aqueous solution of sodium chloride. The organic layer was dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (Carrier: Chromatorex™ NH, elution solvent: heptane-ethyl acetate system) to obtain (E)-1-(6-fluoroindan-1-yl)-3-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)piperidin-2-one as a racemate (200 mg). The compound (200 mg) was fractionated using CHIRALPAK™ AD-H manufactured by Daicel Chemical Industries, Ltd. (2 cm×25 cm: mobile phase: ethanol) to obtain the title optically active substance with a retention time of 7.4 minutes (Example 994, 72 mg; >99% ee) and the title optically active substance with a retention time of 8.4 minutes (Example 993, 68 mg; >96% ee). The physical properties of the compounds are as follows. the organic layer was partitioned The organic layer was washed sequentially with a saturated aqueous solution of ammonium chloride, water The organic layer was dried over anhydrous magnesium sulfate concentrated under reduced pressure The resulting residue was purified by silica gel chromatography (Carrier: Chromatorex™ NH, elution solvent: heptane-ethyl acetate system)

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

Procedure: IPEA (0.58 mL), EDC (0.38 g) and HOBT (0.27 g) were added to a suspension of (E)-5-chloro-2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)valeric acid trifluoroacetate (300 mg) and 6-fluoroindan-1-ylamine (CAS #168902-77-0, 151 mg) in DMF (10 mL) at room temperature, and the reaction solution was stirred at room temperature for 12 hours. A saturated aqueous solution of sodium bicarbonate and ethyl acetate were added to the reaction solution and the organic layer was partitioned. The organic layer was washed sequentially with a saturated aqueous solution of ammonium chloride, water and a saturated aqueous solution of sodium chloride. The organic layer was dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (Carrier: Chromatorex™ NH, elution solvent: heptane-ethyl acetate system) to obtain (E)-5-chloro-2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)valeric acid (6-fluoroindan-1-yl)amide (270 mg). Sodium hydride (containing mineral oil at 40%, 60 mg) was added to a solution of (E)-5-chloro-2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)valeric acid (6-fluoroindan-1-yl)amide (270 mg) in DMF (5 mL) at room temperature, and the reaction solution was stirred at room temperature for 30 minutes. A saturated aqueous solution of sodium bicarbonate and ethyl acetate were added to the reaction solution and the organic layer was partitioned. The organic layer was washed sequentially with a saturated aqueous solution of ammonium chloride, water and a saturated aqueous solution of sodium chloride. The organic layer was dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (Carrier: Chromatorex™ NH, elution solvent: heptane-ethyl acetate system) to obtain (E)-1-(6-fluoroindan-1-yl)-3-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)piperidin-2-one as a racemate (200 mg). The compound (200 mg) was fractionated using CHIRALPAK™ AD-H manufactured by Daicel Chemical Industries, Ltd. (2 cm×25 cm: mobile phase: ethanol) to obtain the title optically active substance with a retention time of 7.4 minutes (Example 994, 72 mg; >99% ee) and the title optically active substance with a retention time of 8.4 minutes (Example 993, 68 mg; >96% ee). The physical properties of the compounds are as follows. the organic layer was partitioned The organic layer was washed sequentially with a saturated aqueous solution of ammonium chloride, water The organic layer was dried over anhydrous magnesium sulfate concentrated under reduced pressure The resulting residue was purified by silica gel chromatography (Carrier: Chromatorex™ NH, elution solvent: heptane-ethyl acetate system)

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

Procedure: The product of Example 135A and Raney/nickel were processed according to the method of Example 131C to provide the product. MS (ESI+) m/z 152 (M+H)+; to provide the product

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

Procedure: Dissolve 6-fluoroindan-1-ylamine (8.50 g, 56.22 mmol) in methanol (200 mL) and triethylamine (8.62 mL, 61.84 mmol). Add 2,6-dichloro-3-nitropyridine (10.85 g, 56.22 mmol) and stir under nitrogen for 14 hours. Filter the reaction mixture and wash the solids with methanol and hexanes to give the title compound as a yellow solid (9.00 g, 52%). MS (ES) m/z=308 [M+1]. Filter the reaction mixture wash the solids with methanol and hexanes

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a high-pressure flask, add 10% palladium on carbon (1.44 g) in ethanol (100 mL). Add a solution of benzyl-(6-fluoroindan-1-yl)-amine (14.44 g, 59.84 mmol) in ethanol (200 mL). Purge the chamber with nitrogen three times, and then with hydrogen three times. Stir vigorously under hydrogen (60 psi) at 50° C. for two hours. Filter the mixture through Celite® 521 and wash the solids with methanol. Concentrate the filtrate in vacuo to give the title compound as a light brown liquid (9.14 g, 100%). MS (ES) m/z=152 [M+1]. Purge the chamber with nitrogen three times Filter the mixture through Celite® 521 wash the solids with methanol Concentrate the filtrate in vacuo

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

Procedure: The title compound was prepared in accordance with the general method described in example 2 from 2-chloro-6-nitro-quinoline and rac-6-fluoro-indan-1-ylamine (CAS no: 168902-77-0); MS: m/e=294.3 (M+H+).

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

Procedure: The product of Example 135A and Raney/nickel were processed according to the method of Example 131C to provide the product. MS (ESI+) m/z 152 (M+H)+; to provide the product

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

Procedure: IPEA (0.58 mL), EDC (0.38 g) and HOBT (0.27 g) were added to a suspension of (E)-5-chloro-2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)valeric acid trifluoroacetate (300 mg) and 6-fluoroindan-1-ylamine (CAS #168902-77-0, 151 mg) in DMF (10 mL) at room temperature, and the reaction solution was stirred at room temperature for 12 hours. A saturated aqueous solution of sodium bicarbonate and ethyl acetate were added to the reaction solution and the organic layer was partitioned. The organic layer was washed sequentially with a saturated aqueous solution of ammonium chloride, water and a saturated aqueous solution of sodium chloride. The organic layer was dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (Carrier: Chromatorex™ NH, elution solvent:heptane-ethyl acetate system) to obtain (E)-5-chloro-2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)valeric acid (6-fluoroindan-1-yl)amide (270 mg). Sodium hydride (containing mineral oil at 40%, 60 mg) was added to a solution of (E)-5-chloro-2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)valeric acid (6-fluoroindan-1-yl)amide (270 mg) in DMF (5 mL) at room temperature, and the reaction solution was stirred at room temperature for 30 minutes. A saturated aqueous solution of sodium bicarbonate and ethyl acetate were added to the reaction solution and the organic layer was partitioned. The organic layer was washed sequentially with a saturated aqueous solution of ammonium chloride, water and a saturated aqueous solution of sodium chloride. The organic layer was dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (Carrier: Chromatorex™ NH, elution solvent:heptane-ethyl acetate system) to obtain (E)-1-(6-fluoroindan-1-yl)-3-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)piperidin-2-one as a racemate (200 mg). The compound (200 mg) was fractionated using CHIRALPAK™ AD-H manufactured by Daicel Chemical Industries, Ltd. (2 cm×25 cm: mobile phase: ethanol) to obtain the title optically active substance with a retention time of 7.4 minutes (Example 994, 72 mg; >99% ee) and the title optically active substance with a retention time of 8.4 minutes (Example 993, 68 mg; >96% ee). The physical properties of the compounds are as follows. the organic layer was partitioned The organic layer was washed sequentially with a saturated aqueous solution of ammonium chloride, water The organic layer was dried over anhydrous magnesium sulfate concentrated under reduced pressure The resulting residue was purified by silica gel chromatography (Carrier: Chromatorex™ NH, elution solvent:heptane-ethyl acetate system)

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

Procedure: IPEA (0.58 mL), EDC (0.38 g) and HOBT (0.27 g) were added to a suspension of (E)-5-chloro-2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)valeric acid trifluoroacetate (300 mg) and 6-fluoroindan-1-ylamine (CAS #168902-77-0, 151 mg) in DMF (10 mL) at room temperature, and the reaction solution was stirred at room temperature for 12 hours. A saturated aqueous solution of sodium bicarbonate and ethyl acetate were added to the reaction solution and the organic layer was partitioned. The organic layer was washed sequentially with a saturated aqueous solution of ammonium chloride, water and a saturated aqueous solution of sodium chloride. The organic layer was dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (Carrier: Chromatorex™ NH, elution solvent: heptane-ethyl acetate system) to obtain (E)-5-chloro-2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)valeric acid (6-fluoroindan-1-yl)amide (270 mg). Sodium hydride (containing mineral oil at 40%, 60 mg) was added to a solution of (E)-5-chloro-2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)valeric acid (6-fluoroindan-1-yl)amide (270 mg) in DMF (5 mL) at room temperature, and the reaction solution was stirred at room temperature for 30 minutes. A saturated aqueous solution of sodium bicarbonate and ethyl acetate were added to the reaction solution and the organic layer was partitioned. The organic layer was washed sequentially with a saturated aqueous solution of ammonium chloride, water and a saturated aqueous solution of sodium chloride. The organic layer was dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (Carrier: Chromatorex™ NH, elution solvent: heptane-ethyl acetate system) to obtain (E)-1-(6-fluoroindan-1-yl)-3-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)piperidin-2-one as a racemate (200 mg). The compound (200 mg) was fractionated using CHIRALPAK™ AD-H manufactured by Daicel Chemical Industries, Ltd. (2 cm×25 cm: mobile phase: ethanol) to obtain the title optically active substance with a retention time of 7.4 minutes (Example 994, 72 mg; >99% ee) and the title optically active substance with a retention time of 8.4 minutes (Example 993, 68 mg; >96% ee). The physical properties of the compounds are as follows. the organic layer was partitioned The organic layer was washed sequentially with a saturated aqueous solution of ammonium chloride, water The organic layer was dried over anhydrous magnesium sulfate concentrated under reduced pressure The resulting residue was purified by silica gel chromatography (Carrier: Chromatorex™ NH, elution solvent: heptane-ethyl acetate system)