2,3-dihydro-1H-inden-2-amine;hydrochloride

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 43.70 g (258 mol) 2-aminoindane hydrochloride and 53.43 g (528 mmol) triethylamine were added to 250 ml of tetrahydrofuran, 42.89 g (270 mmol) 4-fluorobenzoylchloride were added, and the mixture was stirred for 2 h at RT. were added

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 200 ml of dichloromethane, then 15 ml, i.e. 10.9 g (107.6 mmmol) of triethylamine were added to 5 g (29.5 mmol) of 2-aminoindan hydrochloride. The mixture was stirred, then 2.6 ml (29.5 mmol) of propionyl chloride were added and stirring was continued at room temperature for 12 h. Dilute hydrochloric acid was added, the precipitate was filtered, washed, dried and purified by chromatography on a silica gel column, eluted with an 80:20 mixture of dichloromethane/ethyl acetate. 4.87 g of beige solid were isolated. stirring the precipitate was filtered washed dried purified by chromatography on a silica gel column eluted with an 80:20 mixture of dichloromethane/ethyl acetate

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 200 ml of dichloromethane then 10 ml, i.e. 7.26 g (71.7 mmol) of triethylamine were added to 5 g (29.5 mmol) of 2-aminoindan hydrochloride. The mixture was stirred for 30 min, then 3.4 ml, i.e. 3.84 g (35.4 mmol) of ethyl chloroformate were added dropwise. The mixture was stirred for 30 min, then ice-water and an excess of 1N hydrochloric acid were added. The precipitate was filtered, washed, dried and purified by chromatography on a silica gel column, eluted with an 80:20 mixture of dichloromethane/ethyl acetate. 4.25 g of amorphous solid were isolated. The mixture was stirred for 30 min The precipitate was filtered washed dried purified by chromatography on a silica gel column eluted with an 80:20 mixture of dichloromethane/ethyl acetate

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Indanylamine hydrochloride (9.68 g, 57.1 mmol) was added to a suspension of the 4-(N-acetyl-N-methylamino)benzenesulfonyl chloride (12.84 g, 51.9 mmol) prepared in Preparative Example 12 and sodium acetate (18.73 g) in ethanol (100 ml). The obtained mixture was stirred at room temperature for 3 hours, followed by the addition of water. The obtained mixture was extracted with ethyl acetate. The organic layer was washed with water and a saturated aqueous solution of common salt, dried over magnesium sulfate, and concentrated to give N-(2-indanyl)-4-(N-acetyl-N-methylamino)benzenesulfonamide as a white crystal (16.92 g, 95%). Ethanol (80 ml) and 1N aqueous sodium hydroxide (80 ml) were added to the white crystal. The obtained mixture was heated under reflux overnight, acidified with 1N aqueous hydrochloric acid, adjusted to pH 8 with sodium hydrogencarbonate and extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and concentrated to precipitate a crystal. This crystal was recovered by filtration and washed with ether to give the title compound as a white crystal (6.79 g, 46%). The obtained mixture was extracted with ethyl acetate The organic layer was washed with water a saturated aqueous solution of common salt, dried over magnesium sulfate concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Indanylamine hydrochloride (9.68 g, 57.1 mmol) was added to a suspension of the 4-(N-acetyl-N-methylamino)benzenesulfonyl chloride (12.84 g, 51.9 mmol) prepared in Preparative Example 12 and sodium acetate (18.73 g) in ethanol (100 ml). The obtained mixture was stirred at room temperature for 3 hours, followed by the addition of water. The obtained mixture was extracted with ethyl acetate. The organic layer was washed with water and a saturated aqueous solution of common salt, dried over magnesium sulfate, and concentrated to give N-(2-indanyl)-4-(N-acetyl-N-methylamino)benzenesulfonamide as a white crystal (16.92 g, 95%). Ethanol (80 ml) and 1N aqueous sodium hydroxide (80 ml) were added to the white crystal. The obtained mixture was heated under reflux overnight, acidified with 1N aqueous hydrochloric acid, adjusted to pH 8 with sodium hydrogencarbonate and extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and concentrated to precipitate a crystal. This crystal was recovered by filtration and washed with ether to give the title compound as a white crystal (6.79 g, 46%). The obtained mixture was extracted with ethyl acetate The organic layer was washed with water a saturated aqueous solution of common salt, dried over magnesium sulfate concentrated

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mixture of 2-aminoindan hydrochloride (10.40 g), potassium carbonate (34.2 g), water (100 ml) and ethyl acetate (150 ml) is added dropwise acetyl chloride (9.68 g) under ice cooling. The mixture is stirred at 0° C. for 1.5 hour, and the ethyl acetate layer is separated, washed with aqueous saline solution, dried, and then the solvent is distilled off under reduced pressure. The residue is recrystallized from ethyl acetate - n-hexane to give 2-acetylaminoindan (9.5 g) as colorless crystals. m.p. 126.5°-127.5° C. the ethyl acetate layer is separated washed with aqueous saline solution dried the solvent is distilled off under reduced pressure The residue is recrystallized from ethyl acetate - n-hexane

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Acetic anhydride (40 ml) and formic acid (20 ml) were mixed and heated at 50° for 15 minutes with stirring. 2-Aminoindane hydrochloride (25 g) (see J. Med. Chem., 1980, 23, page 745) and sodium acetate (20 g) were added to this mixture which was then stirred at room temperature for 24 hours. The reaction mixture was poured into ice/water and extracted three times with methylene chloride. The combined organic layers were washed with water and aqueous sodium carbonate, dried (MgSO4) and evaporated in vacuo to give the title compound, yield 17.6 g, m.p. 72°-74°. heated at 50° for 15 minutes was then stirred at room temperature for 24 hours extracted three times with methylene chloride The combined organic layers were washed with water and aqueous sodium carbonate dried (MgSO4) evaporated in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: This compound is prepared by the procedure described in EXAMPLE 100 starting from 0.8 g of the compound obtained in EXAMPLE 13, 0.35 g of 2-aminoindane hydrochloride, 0.8 g of BOP, 2 ml of DIPEA and 20 ml of DCM. It is chromatographed on silica using a DCM/AcOEt mixture (96/4; v/v) as the eluent to give 0.7 g of the expected product in the form of white crystals. M.p.=160° C. This compound is prepared by the procedure It is chromatographed on silica using a DCM/AcOEt mixture (96/4; v/v) as the eluent

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: This compound is prepared by the procedure described in EXAMPLE 100 starting from 0.8 g of the compound obtained in EXAMPLE 13, 0.35 g of 2-aminoindane hydrochloride, 0.8 g of BOP, 2 ml of DIPEA and 20 ml of DCM. It is chromatographed on silica using a DCM/AcOEt mixture (96/4; v/v) as the eluent to give 0.7 g of the expected product in the form of white crystals. M.p.=160° C. This compound is prepared by the procedure It is chromatographed on silica using a DCM/AcOEt mixture (96/4; v/v) as the eluent

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 26 g of 2-aminoindane hydrochloride and then 20 g of 4-chloro-1,2-dinitrobenzene are added to a solution of sodium ethylate, prepared from 0.61 g of sodium and 200 ml of EtOH, and the mixture is stirred for 48 hours at RT. The solvent is evaporated off under vacuum, the residue is extracted with AcOEt, washed with water and dried over Na2SO4 and the solvent is evaporated off under vacuum to give 10.3 g of the expected product after crystallization from EtOH. M.p.=108° C. The solvent is evaporated off under vacuum the residue is extracted with AcOEt washed with water dried over Na2SO4 the solvent is evaporated off under vacuum

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 26 g of 2-aminoindane hydrochloride and then 20 g of 4-chloro-1,2-dinitrobenzene are added to a solution of sodium ethylate, prepared from 0.61 g of sodium and 200 ml of EtOH, and the mixture is stirred for 48 hours at RT. The solvent is evaporated off under vacuum, the residue is extracted with AcOEt, washed with water and dried over Na2SO4 and the solvent is evaporated off under vacuum to give 10.3 g of the expected product after crystallization from EtOH. M.p.=108° C. The solvent is evaporated off under vacuum the residue is extracted with AcOEt washed with water dried over Na2SO4 the solvent is evaporated off under vacuum

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Stir a solution of 2,3-dihydro-1H-inden-2-amine hydrochloride (197 g; 1.08 equiv; 1.16 moles), 1H-pyrazole-1-carboximidamide hydrochloride (158 g; 1.00 equiv; 1.08 moles) and diisopropylethylamine (400 g; 2.87 equiv; 3.09 moles; 539.74 mL) in acetonitrile (2 L) at 62° C. for 2 hours, during which time a white solid precipitates. Cool the mixture to 25° C., then filter and wash with 300 mL acetonitrile and 300 mL methyltert-butyl ether. Dry the product in air at 25° C. for 1 h to afford the title compound (200 g, 87%) as a white solid. MS (m/z): 176 (M+1). during which time a white solid precipitates filter wash with 300 mL acetonitrile and 300 mL methyltert-butyl ether Dry the product in air at 25° C. for 1 h