(2,4,6-trimethylphenyl)methanamine

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: A mixture of 3-(2-amino-3-propyl-3,4-dihydro-quinazolin-6-yloxy)-benzoyl chloride (0.0008 mol) in DCM (20 mL) was stirred at 0° C. and 2,4,6-trimethylbenzylamine (0.0013 mol) was added. Then TEA (q.s.) was added, and the reaction mixture was stirred at room temperature. The mixture was stirred in H2O and the organic layer was separated. The remaining layer was washed again with H2O, then the organic layer was separated, dried, and filtered, and the solvent was evaporated. The residue was purified by column chromatography over silica gel (gradient eluent: CH2Cl2:(CH3OH:NH3)). The purest product fractions were collected, and the solvent was evaporated. The residue was triturated under diisopropyl ether:CH3CN, and then the resulting solids were filtered off and dried to yield the title compound as a solid. Then TEA (q.s.) was added the reaction mixture was stirred at room temperature the organic layer was separated The remaining layer was washed again with H2O the organic layer was separated dried filtered the solvent was evaporated The residue was purified by column chromatography over silica gel (gradient eluent: CH2Cl2:(CH3OH:NH3)) The purest product fractions were collected the solvent was evaporated The residue was triturated under diisopropyl ether CH3CN, and then the resulting solids were filtered off dried

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2,4,6-trimethylbenzyl chloride (5 g, 29.7 mmol) in DMSO (20 mL) was added sodium azide (2.9 g, 44.6 mmol). The mixture was heated at 60° C. for 3 h before it was allowed to cool to rt and poured to water (200 mL). The resulted precipitate was filtered dissolved in wet THF (50 mL) followed by the addition of triphenylphosphine (15.6, 59.4 mmol). The mixture was heated under reflux for 3 h and the volatiles were evaporated. The residue was added to 1 N HCl (200 mL) and the solids were filtered off. The filtrate was basified and the resulted precipitate was filtered, dried under vacuum to give 2,4,6-trimethylbenzylamine (2.7 g, 61% yleld). to cool to rt The resulted precipitate was filtered dissolved in wet THF (50 mL) The mixture was heated under reflux for 3 h the volatiles were evaporated The residue was added to 1 N HCl (200 mL) the solids were filtered off the resulted precipitate was filtered dried under vacuum

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

実験手順: The title compound was prepared by using procedures analogous to those described for the synthesis of Intermediate I, using mesitylmethanamine and ethyl 6-bromoimidazo[1,2-a]pyridine-2-carboxylate as starting materials.

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

実験手順: The title compound was prepared by using procedures analogous to those described for the synthesis of Intermediate I, using mesitylmethanamine and ethyl 6-bromoimidazo[1,2-a]pyridine-2-carboxylate as starting materials.

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

実験手順: 3-Hydroxy-benzaldehyde (1.22 g, 0.01 mol) and 2,4,6-trimethyl-benzylamine (1.19 g, 0.01 mol) were added to methanol (10 mL) and the resulting mixture was stirred overnight. Sodium borohydride (0.45 g, 0.012 mol) was then added, and stirring was continued one hour. The resulting mixture was acidified with 2N HCl and then neutralized with saturated aqueous NaHCO3 solution to yield a gummy solution. The gummy solution was extracted with EtOAc (3×100 mL). The organic layer was washed with brine, dried over sodium sulfate, and concentrated in vacuo to yield a white solid. stirring was continued one hour to yield a gummy solution The gummy solution was extracted with EtOAc (3×100 mL) The organic layer was washed with brine dried over sodium sulfate concentrated in vacuo to yield a white solid

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

実験手順: 3-Hydroxy-benzaldehyde (1.22 g, 0.01 mol) and 2,4,6-trimethyl-benzylamine (1.19 g, 0.01 mol) were added to methanol (10 mL) and the resulting mixture was stirred overnight. Sodium borohydride (0.45 g, 0.012 mol) was then added, and stirring was continued one hour. The resulting mixture was acidified with 2N HCl and then neutralized with saturated aqueous NaHCO3 solution to yield a gummy solution. The gummy solution was extracted with EtOAc (3×100 mL). The organic layer was washed with brine, dried over sodium sulfate, and concentrated in vacuo to yield a white solid. stirring was continued one hour to yield a gummy solution The gummy solution was extracted with EtOAc (3×100 mL) The organic layer was washed with brine dried over sodium sulfate concentrated in vacuo to yield a white solid

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

実験手順: 6-(3-[1,3]Dioxan-2-yl-phenylsulfanyl)-3-(tetrahydro-pyran-4-ylmethyl)-quinolin-2-ylamine (40 mg, 0.1 mmol) was dissolved in acetic acid (1 mL) and then 2,4,6-trimethylbenzyl amine (0.1 g, 0.67 mmol) was added. The resulting mixture was subjected to μwave @ 300W, 100° C. for 12 min. The resulting mixture was evaporated under reduced pressure (high vacuum) overnight. Methanol (2 mL) was added, followed by addition of NaBH4 (0.2 g, 5.2 mmol, portionwise) over 1.5 h. The solvent was removed to yield a residue, to which was added 0.1 N NaOH (5 ml). The resulting mixture was extracted with chloroform (3×). The organic layers were combined and dried with MgSO4 and then filtered. The solvent was removed to yield the title compound as a residue, which was purified by reverse phase chromatography (10-90% CH3CN/H2O/0.1% TFA). The product containing fractions were treated with 1N HCl (1 mL) to yield the title compound, 3-(tetrahydro-pyran-4-ylmethyl)-6-{3-[(2,4,6-trimethyl-benzylamino)-methyl]-phenylsulfanyl}-quinolin-2-ylamine, as a residue. for 12 min The resulting mixture was evaporated under reduced pressure (high vacuum) overnight Methanol (2 mL) was added followed by addition of NaBH4 (0.2 g, 5.2 mmol The solvent was removed to yield a residue The resulting mixture was extracted with chloroform (3×) dried with MgSO4 filtered The solvent was removed

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

実験手順: A mixture of 3-(2-amino-3-propyl-3,4-dihydro-quinazolin-6-yloxy)-benzoyl chloride (0.0008 mol) in DCM (20 mL) was stirred at 0° C. and 2,4,6-trimethylbenzylamine (0.0013 mol) was added. Then TEA (q.s.) was added, and the reaction mixture was stirred at room temperature. The mixture was stirred in H2O and the organic layer was separated. The remaining layer was washed again with H2O, then the organic layer was separated, dried, and filtered, and the solvent was evaporated. The residue was purified by column chromatography over silica gel (gradient eluent: CH2Cl2:(CH3OH:NH3)). The purest product fractions were collected, and the solvent was evaporated. The residue was triturated under diisopropyl ether:CH3CN, and then the resulting solids were filtered off and dried to yield the title compound as a solid. Then TEA (q.s.) was added the reaction mixture was stirred at room temperature the organic layer was separated The remaining layer was washed again with H2O the organic layer was separated dried filtered the solvent was evaporated The residue was purified by column chromatography over silica gel (gradient eluent: CH2Cl2:(CH3OH:NH3)) The purest product fractions were collected the solvent was evaporated The residue was triturated under diisopropyl ether CH3CN, and then the resulting solids were filtered off dried

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

実験手順: A mixture of 3-(2-amino-3-propyl-3,4-dihydro-quinazolin-6-yloxy)-benzoyl chloride (0.0008 mol) in DCM (20 mL) was stirred at 0° C. and 2,4,6-trimethylbenzylamine (0.0013 mol) was added. Then TEA (q.s.) was added, and the reaction mixture was stirred at room temperature. The mixture was stirred in H2O and the organic layer was separated. The remaining layer was washed again with H2O, then the organic layer was separated, dried, and filtered, and the solvent was evaporated. The residue was purified by column chromatography over silica gel (gradient eluent: CH2Cl2:(CH3OH:NH3)). The purest product fractions were collected, and the solvent was evaporated. The residue was triturated under diisopropyl ether:CH3CN, and then the resulting solids were filtered off and dried to yield the title compound as a solid. Then TEA (q.s.) was added the reaction mixture was stirred at room temperature the organic layer was separated The remaining layer was washed again with H2O the organic layer was separated dried filtered the solvent was evaporated The residue was purified by column chromatography over silica gel (gradient eluent: CH2Cl2:(CH3OH:NH3)) The purest product fractions were collected the solvent was evaporated The residue was triturated under diisopropyl ether CH3CN, and then the resulting solids were filtered off dried

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2,4,6-trimethylbenzyl chloride (5 g, 29.7 mmol) in DMSO (20 mL) was added sodium azide (2.9 g, 44.6 mmol). The mixture was heated at 60° C. for 3 h before it was allowed to cool to rt and poured to water (200 mL). The resulted precipitate was filtered dissolved in wet THF (50 mL) followed by the addition of triphenylphosphine (15.6, 59.4 mmol). The mixture was heated under reflux for 3 h and the volatiles were evaporated. The residue was added to 1 N HCl (200 mL) and the solids were filtered off. The filtrate was basified and the resulted precipitate was filtered, dried under vacuum to give 2,4,6-trimethylbenzylamine (2.7 g, 61 % yield). to cool to rt The resulted precipitate was filtered dissolved in wet THF (50 mL) The mixture was heated under reflux for 3 h the volatiles were evaporated The residue was added to 1 N HCl (200 mL) the solids were filtered off the resulted precipitate was filtered dried under vacuum