2,4,6-tris[(dimethylamino)methyl]phenol

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

Procedure: To a DMF 3 mL solution of product obtained in step A (410 mg, 1.58 mmol) were added 4-(2,4,6-trifluoro-benzoyl)-1H-pyrrole-2-carboxylic acid (427 mg, 1.58 mmol), EDC (396 mg, 2.06 mmol), HOBt (316 mg, 2.06 mmol) and triethylamine (0.443 mL, 3.17 mmol). The reaction mixture was stirred overnight at room temperature. The resulting suspension was filtered and diluted with EtOAc, washed with sat. ammonium chloride aq., sat. sodium bicarbonate aq. and brine, dried over anhydrous Na2SO4, filtered and concentrated to give the title compound as foam (430 mg). LC/MS: m/z 510(M+H). The resulting suspension was filtered diluted with EtOAc washed with sat. ammonium chloride aq., sat. sodium bicarbonate aq. and brine dried over anhydrous Na2SO4 filtered concentrated

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

Procedure: To a DMF 3 mL solution of product obtained in step A (410 mg, 1.58 mmol) were added 4-(2,4,6-trifluoro-benzoyl)-1H-pyrrole-2-carboxylic acid (427 mg, 1.58 mmol), EDC (396 mg, 2.06 mmol), HOBt (316 mg, 2.06 mmol) and triethylamine (0.443 mL, 3.17 mmol). The reaction mixture was stirred overnight at room temperature. The resulting suspension was filtered and diluted with EtOAc, washed with sat. ammonium chloride aq., sat. sodium bicarbonate aq. and brine, dried over anhydrous Na2SO4, filtered and concentrated to give the title compound as foam (430 mg). LC/MS: m/z 510(M+H). The resulting suspension was filtered diluted with EtOAc washed with sat. ammonium chloride aq., sat. sodium bicarbonate aq. and brine dried over anhydrous Na2SO4 filtered concentrated

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

Procedure: To a DMF 3 mL solution of 2-{[(tert-butoxycarbonyl)amino]methyl}-3H-imidazo[4,5-b]pyridine-6-carboxylic acid (293 mg, 1.0 mmol) were added HOBt (162 mg, 1.2 mmol), 2,2,2-trifluoroethanamine (130 mg, 1.5 mmol), DIPEA (388 mg, 3.0 mmol) and EDC (288 mg, 1.5 mmol). The reaction mixture was stirred at room temperature overnight and was partitioned between EtOAc and water. The organic layer was washed with brine twice, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The residue was purified by prep TLC (MeOH/CH2Cl2=1/10, v/v) to give the title compound (0.26 g, 70%). was partitioned between EtOAc and water The organic layer was washed with brine twice dried over anhydrous Na2SO4 concentrated under reduced pressure The residue was purified by prep TLC (MeOH/CH2Cl2=1/10

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 5-isoquinolinethiol 220 mg (1.4 mmol), 6-fluoro-7-nitroquinoxaline 260 mg (1.4 mmol), potassium carbonate 380 mg (2.7 mmol) and DMF 3 ml was stirred for 2 hours at 100° C. The reaction solution was poured into water, the precipitates were collected and washed with water, and 6-(5-isoquinolylthio)-7-nitroquinoxaline 410 mg (90.4%) was obtained. the precipitates were collected washed with water

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 50 ml round-bottom flask were added ethyl 7-hydroxychromane-2-carboxylate (100 mg, 0.45 mmol), 4-(3-bromopropoxy)-3-propylphenyl phenyl ether (U.S. Pat. No. 6,008,237) (188 mg, 0.54 mmol), cesium carbonate (176 mg, 0.54 mmol), and DMF 3 ml. The resulting suspension was stirred at 70° C. for 5 hr. The solvent was removed under reduced pressure. The residue was diluted with AcOEt and water. The organic layer was separated. The aqueous layer was extracted twice with AcOEt. The combined organic layers were dried over anhydrous Na2SO4, filtered, concentrated, and chromatographed on silica gel. Eluting with 10% AcOEt/hexanes gave the title compound as a pale yellow oil 167 mg (76%). The solvent was removed under reduced pressure The residue was diluted with AcOEt and water The organic layer was separated The aqueous layer was extracted twice with AcOEt The combined organic layers were dried over anhydrous Na2SO4 filtered concentrated chromatographed on silica gel Eluting with 10% AcOEt/hexanes

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 50 ml round-bottom flask were added ethyl 7-hydroxychromane-2-carboxylate (100 mg, 0.45 mmol), 4-(3-bromopropoxy)-3-propylphenyl phenyl ether (U.S. Pat. No. 6,008,237) (188 mg, 0.54 mmol), cesium carbonate (176 mg, 0.54 mmol), and DMF 3 ml. The resulting suspension was stirred at 70° C. for 5 hr. The solvent was removed under reduced pressure. The residue was diluted with AcOEt and water. The organic layer was separated. The aqueous layer was extracted twice with AcOEt. The combined organic layers were dried over anhydrous Na2SO4, filtered, concentrated, and chromatographed on silica gel. Eluting with 10% AcOEt/hexanes gave the title compound as a pale yellow oil 167 mg (76%). The solvent was removed under reduced pressure The residue was diluted with AcOEt and water The organic layer was separated The aqueous layer was extracted twice with AcOEt The combined organic layers were dried over anhydrous Na2SO4 filtered concentrated chromatographed on silica gel Eluting with 10% AcOEt/hexanes

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

Procedure: Analogously to Example 19, starting from 53.1 g (0.2 mol) of 2,4,6-tris(dimethylaminomethyl)phenol and 9.2 g (0.2 mol) of lithium hydroxide there are obtained 54.3 g of lithium 2,4,6-tris(dimethylaminomethyl)phenolate in the form of an orange solid of which the elemental analysis is as follows:

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

Procedure: 53.1 g (0.2 mol) of 2,4,6-tris(dimethylaminomethyl)phenol and 100 ml of H2O are placed in a 500 ml round-bottomed flask having a magnetic stirrer and dropping funnel and, with stirring, 16.0 g (0.2 mol) of a 50% aqueous NaOH solution are added dropwise thereto. The clear, slightly yellow solution is concentrated by evaporation in a rotary evaporator at 70° C., and the residue is dried at 100° C./125 T (16.6×103Pa), yielding 55.1 g of sodium 2,4,6-tris(dimethylaminomethyl)phenolate in the form of a brownish solid of which the elemental analysis is as follows: The clear, slightly yellow solution is concentrated by evaporation in a rotary evaporator at 70° C. the residue is dried at 100° C./125 T (16.6×103Pa)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 106.16 g (0.4 mol) of 2,4,6-tris(dimethylaminomethyl)phenol and 13.58 g (0.04 mol) of tetrabutylammonium hydrogen sulfate are placed in 200 ml of toluene in a 750 ml sulfonating flask having an anchor mixer, thermometer, reflux condenser and dropping funnel and at RT 80 g (1.0 tool) of a 50% aqueous NaOH solution are added dropwise in the course of 30 minutes. The suspension is then stirred for 30 minutes at 80° C. and then at the same temperature 154.5 g (0.8 mol) of octyl bromide are added in the course of 45 minutes. After a subsequent reaction period of 2 hours the mixture is cooled and filtered, and the filtrate is washed once with 30 ml of H20, dried over MgSO4, filtered and concentrated by evaporation, yielding 137.4 g of 2,4,6-tris(dimethylaminomethyl)phenyloctyl ether in the form of a brown, highly viscous liquid which no longer has an 0H band in the IR spectrum and of which the NMR analysis is in agreement with the said structure. thermometer, reflux condenser After a subsequent reaction period of 2 hours the mixture is cooled filtered the filtrate is washed once with 30 ml of H20 dried over MgSO4 filtered concentrated by evaporation

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 53.1 g (0.2 mol) of 2,4,6-tris(dimethylaminomethyl)phenol and 6.8 g (0.02 mol) of tetrabutylammonium hydrogen sulfate are placed in 100 ml of toluene in a 350 ml sulfonating flask having an anchor mixer, thermometer, reflux condenser and dropping funnel and at RT 40 g (0.5 tool) of a 50% aqueous NaOH solution are added dropwise in the course of 30 minutes. The suspension is then stirred for 30 minutes at 80° C. and then at the same temperature 54.8 g (0.4 mol) of butyl bromide are added in the course of 45 minutes. After a subsequent reaction period of 3 hours the mixture is cooled and filtered, and the filtrate is washed once with 30 ml of H2O, dried over MgSO4, filtered and concentrated by evaporation, yielding 48 g of 2,4,6-tris(dimethylaminomethyl)phenylbutyl ether in the form of a brown liquid which no longer has an OH band in the IR spectrum and of which the NMR analysis is in agreement with the said structure. thermometer, reflux condenser After a subsequent reaction period of 3 hours the mixture is cooled filtered the filtrate is washed once with 30 ml of H2O dried over MgSO4 filtered concentrated by evaporation

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

Procedure: Analogously to Example 19, starting from 53.1 g (0.2 mol) of 2,4,6-tris(dimethylaminomethyl)phenol and 9.2 g (0.2 mol) of lithium hydroxide there are obtained 54.3 g of lithium 2,4,6-tris(dimethylaminomethyl)phenolate in the form of an orange solid of which the elemental analysis is as follows:

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

Procedure: 53.1 g (0.2 mol) of 2,4,6-tris(dimethylaminomethyl)phenol and 100 ml of H2O are placed in a 500 ml round-bottomed flask having a magnetic stirrer and dropping funnel and, with stirring, 16.0 g (0.2 mol) of a 50% aqueous NaOH solution are added dropwise thereto. The clear, slightly yellow solution is concentrated by evaporation in a rotary evaporator at 70° C., and the residue is dried at 100° C./125 T (16.6×103Pa), yielding 55.1 g of sodium 2,4,6-tris(dimethylaminomethyl)phenolate in the form of a brownish solid of which the elemental analysis is as follows: The clear, slightly yellow solution is concentrated by evaporation in a rotary evaporator at 70° C. the residue is dried at 100° C./125 T (16.6×103Pa)