5-bromo-3,4-dihydro-2H-naphthalen-1-one

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: 8.5 of 5-bromotetralone are dissolved in 100 ml of ethanol, and 25 ml of a 33% solution of methylamine in ethanol are added. The mixture is cooled to 5° and the pH is adjusted to 6-7 with acetic acid. Then 2.5 g of sodium cyanoborohydride are added in portions. The reaction mixture is then stirred at room temperature during 36 hours. The solvent is evaporated and the residue is added to 1N NaOH. The aqueous phase is extracted 3× with ether and the combined organic extracts are dried on Na2SO4 and evaporated. The remaining oil (8.7 g) is dissolved in 100 ml of methanol and 6 ml of a 33% aqueous solution of formaldehyde are added. The mixture is cooled to 5° and 2.8 g of sodium borohydride are added. After stirring at room temperature for 24 hours, the reaction mixture is concentrated and the residue is added to 1N HCl. The aqueous phase is washed 2× with ether. The pH is then adjusted to 10 with 30% NaOH and extraction follows 3× with ether. The organic extracts are dried on Na2SO4 and concentrated. The 5-bromo-N,N-dimethyl-1,2,3,4-tetrahydro-1-naphthalenylamine is obtained. The mixture is cooled to 5° The solvent is evaporated the residue is added to 1N NaOH The aqueous phase is extracted 3× with ether the combined organic extracts are dried on Na2SO4 evaporated The remaining oil (8.7 g) is dissolved in 100 ml of methanol 6 ml of a 33% aqueous solution of formaldehyde are added The mixture is cooled to 5° 2.8 g of sodium borohydride are added After stirring at room temperature for 24 hours the reaction mixture is concentrated the residue is added to 1N HCl The aqueous phase is washed 2× with ether The pH is then adjusted to 10 with 30% NaOH and extraction The organic extracts are dried on Na2SO4 concentrated

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

実験手順: 0.41 g (4.5 mmol) of copper(I) cyanide is added to a solution of 1.0 g (4.4 mmol) of 5-bromo-1-tetralone [see J. Org. Chem. 49, 4226 (1984)] in 1.3 ml of DMF, and the reaction mixture is stirred at 160° for 6 hours. The reaction mixture is then cooled to 80°, and a solution of 1.6 g of iron(III) chloride hexahydrate in 2.5 ml of water and 0.44 ml of concentrated hydrochloric acid is added. Stirring is continued for 45 minutes, the reaction mixture is cooled and diluted with water, and extraction is carried out with toluene. The organic phase is washed with water, dried over magnesium sulfate, filtered and concentrated by evaporation. In that manner there is obtained the title compound in the form of yellow-orange crystals, IR (CH2Cl2): 2220, 1690 cm-1 ; 1H-NMR (CDCl3): δ=8.26 (q,1H); 7.81 (q,1H); 7.43 (t,1H); 3.21 (t,2H); 2.72 (t,2H); 2.23 (m,2H). The reaction mixture is then cooled to 80° Stirring is continued for 45 minutes the reaction mixture is cooled The organic phase is washed with water dried over magnesium sulfate filtered concentrated by evaporation

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 5-bromo-3,4-dihydronaphthalen-1(2H)-one (9.95 g, 44.2 mmol) in NMP (50 mL) was added Zn(CN)2 (10.38 g, 88.4 mmol). The mixture was degassed twice by bubbling N2 through the solution for 30 min then evacuated. Pd(Ph3)4 (0.5 g, 0.44 mmol) was added and the mixture was heated to 110° C. under N2. After 5 h, the mixture was cooled to room temperature and poured onto ice (600 mL), using water (300 mL) to complete the transfer. After the ice had melted, the solution was filtered and the resulting solid was collected, suspended in DCM, and filtered again. The solid was collected, washed with water, and purified by column chromatography (EA/hex) to provide 6.9 g (91%) of 5-oxo-5,6,7,8-tetrahydronaphthalene-1-carbonitrile INT-1 as a white solid. LCMS-ESI (m/z) calculated for C11H9NO: 171.2; found 172.1 [M+H]+, tR=2.95 min. 1H NMR (400 MHz, CDCl3) δ 8.26 (dd, J=7.9, 1.4 Hz, 1H), 7.82 (dd, J=7.6, 1.4 Hz, 1H), 7.44 (t, J=7.8 Hz, 1H), 3.20 (t, J=6.1 Hz, 2H), 2.72 (dd, J=7.2, 6.1 Hz, 2H), 2.30-2.17 (m, 2H). 13C NMR (101 MHz, CDCl3) δ 196.22, 147.39, 137.18, 133.39, 131.59, 127.19, 116.93, 112.94, 38.48, 28.05, 22.28. The mixture was degassed twice by bubbling N2 through the solution for 30 min then evacuated the mixture was cooled to room temperature poured onto ice (600 mL) the solution was filtered the resulting solid was collected filtered again The solid was collected washed with water purified by column chromatography (EA/hex)

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

実験手順: To a benzene solution (60 ml) of 4-(o-bromophenyl) butyric acid (5 g) was added oxalyl chloride (3.6 ml) and the reaction refluxed for 11/2 hrs. The solution was evaporated to dryness, the residue was dissolved in CH2Cl2 (50 ml) then cooled to 0° C., followed by the addition of AlCl3 (3.1 g). The mixture was stirred at 0° C. warming to room temperature overnight. The reaction was poured onto ice, then extracted with CH2Cl2. The organic layer was separated, washed with 1 N NaOH, then brine, separated, dried (MgSO4), filtered and evaporated affording the desired product (4.26 g). the reaction refluxed for 11/2 hrs The solution was evaporated to dryness the residue was dissolved in CH2Cl2 (50 ml) followed by the addition of AlCl3 (3.1 g) warming to room temperature overnight The reaction was poured onto ice extracted with CH2Cl2 The organic layer was separated washed with 1 N NaOH brine, separated dried (MgSO4) filtered evaporated

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

実験手順: 2-Bromobenzyl bromide was converted into 5-bromotetralone according to the literature (J. Org. Chem. 1984, p4226). Treatment of 5-bromotetralone with selenium dioxide as described in Referene Example 1A yielded 5-bromo-[1,2]naphthoquinone, which was coupled with 2,3-diamino-benzoic acid, diacetate salt, as described in Reference Example 1A to yield the title compound.

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

実験手順: To a benzene solution (60 ml) of 4-(o-bromophenyl) butyric acid (5 g) was added oxalyl chloride (3.6 ml) and the reaction refluxed for 11/2 hrs. The solution was evaporated to dryness, the residue was dissolved in CH2Cl2 (50 ml) then cooled to 0° C., followed by the addition of AlCl3 (3.1 g). The mixture was stirred at 0° C. warming to room temperature overnight. The reaction was poured onto ice, then extracted with CH2Cl2. The organic layer was separated, washed with 1N NaOH, then brine, separated, dried (MgSO4), filtered and evaporated affording the desired product (4.26 g). the reaction refluxed for 11/2 hrs The solution was evaporated to dryness the residue was dissolved in CH2Cl2 (50 ml) followed by the addition of AlCl3 (3.1 g) warming to room temperature overnight The reaction was poured onto ice extracted with CH2Cl2 The organic layer was separated washed with 1N NaOH brine, separated dried (MgSO4) filtered evaporated

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

実験手順: 8.5 of 5-bromotetralone are dissolved in 100 ml of ethanol, and 25 ml of a 33% solution of methylamine in ethanol are added. The mixture is cooled to 5° and the pH is adjusted to 6-7 with acetic acid. Then 2.5 g of sodium cyanoborohydride are added in portions. The reaction mixture is then stirred at room temperature during 36 hours. The solvent is evaporated and the residue is added to 1N NaOH. The aqueous phase is extracted 3× with ether and the combined organic extracts are dried on Na2SO4 and evaporated. The remaining oil (8.7 g) is dissolved in 100 ml of methanol and 6 ml of a 33% aqueous solution of formaldehyde are added. The mixture is cooled to 5° and 2.8 g of sodium borohydride are added. After stirring at room temperature for 24 hours, the reaction mixture is concentrated and the residue is added to 1N HCl. The aqueous phase is washed 2× with ether. The pH is then adjusted to 10 with 30% NaOH and extraction follows 3× with ether. The organic extracts are dried on Na2SO4 and concentrated. The 5-bromo-N,N-dimethyl-1,2,3,4-tetrahydro-1-naphthalenylamine is obtained. The mixture is cooled to 5° The solvent is evaporated the residue is added to 1N NaOH The aqueous phase is extracted 3× with ether the combined organic extracts are dried on Na2SO4 evaporated The remaining oil (8.7 g) is dissolved in 100 ml of methanol 6 ml of a 33% aqueous solution of formaldehyde are added The mixture is cooled to 5° 2.8 g of sodium borohydride are added After stirring at room temperature for 24 hours the reaction mixture is concentrated the residue is added to 1N HCl The aqueous phase is washed 2× with ether The pH is then adjusted to 10 with 30% NaOH and extraction The organic extracts are dried on Na2SO4 concentrated