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(R)-6-chloro-4-fluoroindan-1-ylamine hydrochloride[ No CAS ]
[ 128798-39-0 ]
[ 100-52-7 ]
2-nitro-N-[(R)-carbamoylphenylmethyl]-N-[(R)-6-chloro-4-fluoroindan-1-yl]nicotinamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
0.09 g
Example 13 2-Amino-N-[(R)-carbamoylphenylmethyl]-N-[(R)-6-chloro-4-fluoroindan-1-yl]nicotinamide To a solution of (R)-6-chloro-4-fluoroindan-1-ylamine hydrochloride (0.1 g) in methanol (3 mL) were added triethylamine (0.046 g) and benzaldehyde (0.048 g), and the mixture was stirred for 0.5 hours at 65° C. The reaction mixture was allowed to cool to room temperature, and to the mixture were added <strong>[33225-72-8]2-nitronicotinic acid</strong> (0.083 g) and 4-phenylcyclohexen-1-ylisocyanide (0.083 g). The mixture was stirred overnight at 65° C., then allowed to cool to room temperature, and concentrated under reduced pressure. To the obtained residue were added tetrahydrofuran (4 mL), water (40 muL) and a solution of 4 mol/L hydrogen chloride in 1,4-dioxane (340 muL), and the mixture was stirred for 1 hour at room temperature. To the reaction mixture were added water and a saturated aqueous solution of sodium bicarbonate, and the crude product was extracted with ethyl acetate. The organic layer was washed with water and brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: methanol/ethyl acetate/n-hexane=0/60/40 to 0/100/0 to 20/80/0) to afford 2-nitro-N-[(R)-carbamoylphenylmethyl]-N-[(R)-6-chloro-4-fluoroindan-1-yl]nicotinamide (0.090 g). A suspension of Raney catalyst was prepared as follows. A mixture of Raney (registered trademark) 2800 nickel slurry in water, active catalyst (Sigma-Aldrich) (200 muL) and ethanol was stirred, and the solvent was removed by decantation. The catalyst was washed 3 times with ethanol, and ethanol (1 mL) was added to form a suspension.
0.09 g
Triethylamine (0.046g) and benzaldehyde (0.048g) in addition to methanol (3mL) solution of (R) -6- chloro-4-fluoro-indan-1-ylamine hydrochloride(0.1g), at 65 It was stirred for 0.5 hours. The reaction mixture was allowed to cool to room temperature, <strong>[33225-72-8]2-nitro-nicotinic acid</strong> (0.083 g) and4-phenyl-cyclohexen-1-yl isocyanide a (0.083 g) was added and stirred overnight at 65 ° C.. After the reaction mixture was allowed to cool to roomtemperature, and then concentrated under reduced pressure. The obtained residue in tetrahydrofuran (4 mL), water (40 muL) and 4 mol / Lhydrogen chloride in 1,4-dioxane solution (340muL) was added, and stirred for 1 hour at room temperature. Water and saturated sodium bicarbonatesolution was added to the reaction mixture, the crude product was extracted with ethyl acetate. The organic layer was washed with water and brine,dried over anhydrous magnesium sulfate. The solvent was obtained by vacuum distillation residue was purified by silica gel column chromatography(eluting solvent methanol / ethyl acetate / n-hexane = 0/60 / 40-0 / 100 / 0-20 / 80/0), 2-nitro -N - [(R) - carbamoyl phenylmethyl] -N - was obtained[(R) -6- chloro-4-fluoro-indan-1-yl] nicotinamide (0.090 g). A suspension of Raney catalysts were prepared as follows. Raney (TM) 2800 nickel, slurryin water, stirring the mixture of ethanol and a suspension (200 muL) of active catalyst (Sigma-Aldrich), and the solvent was removed by decantation.The catalyst was washed 3 times with ethanol, ethanol (1 mL) was added and the suspension. The Raney catalyst suspension, under an argonatmosphere, 2-nitro -N - [(R) - carbamoyl phenylmethyl] -N - [(R) -6- chloro-4-fluoro-indan-1-yl] nicotinamide It added at room temperature in ethanol(1mL) solution of (0.090g), and the mixture was stirred under a hydrogen atmosphere for 5 hours. The catalyst was removed by filtration, and thefiltrate was concentrated under reduced pressure. The residue aminopropyl silica gel column chromatography (eluting solvent ethyl acetate /n-hexane = 90 / 10-100 / 0) to give the title compound (0.071 g).
(R)-6-chloro-4-fluoroindan-1-ylamine hydrochloride[ No CAS ]
[ 128798-39-0 ]
[ 100-52-7 ]
C35H30ClFN4O4[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
To a solution of (R)-6-chloro-4-fluoroindan-1-ylamine hydrochloride (0.1 g) in methanol (3 mL) were added triethylamine (0.046 g) and benzaldehyde (0.048 g), and the mixture was stirred for 0.5 hours at 65° C. The reaction mixture was allowed to cool to room temperature, and to the mixture were added <strong>[33225-72-8]2-nitronicotinic acid</strong> (0.083 g) and 4-phenylcyclohexen-1-ylisocyanide (0.083 g). The mixture was stirred overnight at 65° C., then allowed to cool to room temperature, and concentrated under reduced pressure. To the obtained residue were added tetrahydrofuran (4 mL), water (40 muL) and a solution of 4 mol/L hydrogen chloride in 1,4-dioxane (340 muL), and the mixture was stirred for 1 hour at room temperature. To the reaction mixture were added water and a saturated aqueous solution of sodium bicarbonate, and the crude product was extracted with ethyl acetate. The organic layer was washed with water and brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: methanol/ethyl acetate/n-hexane=0/60/40 to 0/100/0 to 20/80/0) to afford 2-nitro-N--[(R)-carbamoylphenylmethyl]-N--[(R)-6-chloro-4-fluoroindan-1-y- l]nicotinamide (0.090 g). A suspension of Raney catalyst was prepared as follows. A mixture of Raney (registered trademark) 2800 nickel slurry in water, active catalyst (Sigma-Aldrich) (200 muL) and ethanol was stirred, and the solvent was removed by decantation. The catalyst was washed 3 times with ethanol, and ethanol (1 mL) was added to form a suspension. To a solution of 2-nitro-N--[(R)-carbamoylphenylmethyl]-N--[(R)-6-chloro-4-fluoroindan-1-y- l]nicotinamide (0.090 g) in ethanol (1 mL) was added the suspension of Raney catalyst at room temperature, and the mixture was stirred for 5 hours under hydrogen atmosphere. The catalyst was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by aminopropyl silica gel column chromatography (eluent:ethyl acetate/n-hexane=90/10 to 100/0) to afford the title compound (0.071 g).
Compound 3 (16.8 g, 0.1 mol) was dissolved in acetonitrile (100 mL).Add 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (24.9 g, 0.13 mol),Stir at room temperature for 2 hours.Compound 2 (17.18 g, 0.13 mol) was added,The temperature was raised to 90 ° C and kept for 6 hours.After completion of the reaction, the acetonitrile was evaporated to give an oily substance, and purified water (80 ml) was added thereto, and the mixture was stirred, and filtered, and rinsed with water.Compound 4 and dried to give 26.42g, 93.6percent yield
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