4-(dimethylamino)benzenethiol

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:135.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a pressure reactor was placed 5-bromo-N-(2,3-dimethoxybenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide (0.1 g, 0.24 mmol), 4-(dimethylamino)benzenethiol (0.147 g, 0.96 mmol) and triethylamine (0.363 g, 0.5 mL, 3.59 mmol). The vessel was purged with nitrogen gas, sealed and heated to 135° C. for 18 hours, after which time it was cooled and the excess triethylamine removed in vacuo. The residue was partitioned between EtOAc/water and extracted. The combined organic extracts were washed with brine, dried over Na2SO4, filtered and the solvent removed. The resulting glass was triturated with diethyl ether and filtered to yield N-(2,3-dimethoxybenzyl)-5-{[4-(dimethylamino)phenyl]thio}-8-hydroxy-1,6-naphthyridine-7-carboxamide as a solid. Into a pressure reactor was placed The vessel was purged with nitrogen gas sealed after which time it was cooled the excess triethylamine removed in vacuo The residue was partitioned between EtOAc/water extracted The combined organic extracts were washed with brine dried over Na2SO4 filtered the solvent removed The resulting glass was triturated with diethyl ether filtered

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-bromo-2-methylpent-2-enoic acid methyl ester (0.414 g, 2.0 mmol) in dry benzene (4 mL) under an atmosphere of argon was added a solution of triethylamine (0.28 mL, 2.0 mmol) and 4-dimethylamino-benzenethiol (0.306 g, 2.0 mmol) in dry benzene (2 mL). The mixture was stirred at 20° C. for 2 hours (TLC monitoring). The solvent was then removed under reduced pressure to give a yellow oil that was purified by column chromatography (20:79:1 diethyl ether:60-80° C. petroleum ether:triethylamine) to give the title compound (0.53 g, 95%) as a colourless oil. The solvent was then removed under reduced pressure to give a yellow oil that was purified by column chromatography (20:79:1 diethyl ether:60-80° C. petroleum ether:triethylamine)

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 6-bromo-hexa-2,4-dienoic acid methyl ester (1.15 g, 5.6 mmol) and 4-dimethylamino-benzenethiol (0.86 g, 5.6 mmol) in tetrahydrofuran (30 mL) was added dropwise triethylamine (1.6 mL, 11.4 mmol) under an atmosphere of argon. The mixture was stirred at 20° C. for 30 minutes, then filtered. The filtrate was concentrated under reduced to pressure and the residue was dissolved in ethyl acetate (100 mL). This solution was washed with saturated aqueous sodium hydrogen carbonate (50 mL), demineralised water (50 mL) and brine (50 mL). The organic layer was dried over anhydrous MgSO4, filtered and concentrated under reduced pressure to give a yellow oil that was purified by column chromatography (9:1 to 7:3 60-80° C. petroleum ether:diethyl ether, all eluant containing 1% triethylamine by volume). The solid was recrystallised from diethyl ether/petroleum ether to give the title compound (1.0 g, 64%) as a white solid, mp 68-70° C. filtered The filtrate was concentrated the residue was dissolved in ethyl acetate (100 mL) This solution was washed with saturated aqueous sodium hydrogen carbonate (50 mL), demineralised water (50 mL) and brine (50 mL) The organic layer was dried over anhydrous MgSO4 filtered concentrated under reduced pressure to give a yellow oil that was purified by column chromatography (9:1 to 7:3 60-80° C. petroleum ether diethyl ether, all eluant containing 1% triethylamine by volume) The solid was recrystallised from diethyl ether/petroleum ether

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

Procedure: Trans-2-[3-n-propylsulfonyl-4-(2-bromoethoxy)-5-methoxyphenyl)-5-(3,4,5-trimethoxyphenyl)tetrahydrofuran (100 mg) (Step 30G) was added to a stirred solution of 4-dimethylaminothiophenol (76 mg, 0.5 mmol) and sodium hydride (56%; 20 mg, 0.5 mmol) in DMF (1 mL). The reaction mixture was stirred at room temperature for 20 min and partitioned between ethyl ether and water. The organic layer was separated, dried, and evaporated to a crystalline mass. Recrystallized from ethyl ether-hexane gave pure product: mp 113°-115° C.; NMR (CDCl3) δ 1.0 (t, CH2CH2CH3), 1.70 (m, CH2CH2CH3), 2.0 & 2.49 (2 m, H-3 & H-4), 3.0 [m, (CH3)2N], 3.4 (m, CH2CH2CH3), 3.84 3.88 & 3.9 (3 s, 3 OCH3), 4.30 (t, SCH2CH2O), 5.22 (m, H-2 & H-5), 6.62 (s, C5ArH), 7.23 & 7.47 (2 d, J=1.5 Hz, C2ArH), 7.42 (m, ArH). partitioned between ethyl ether and water The organic layer was separated dried evaporated to a crystalline mass Recrystallized from ethyl ether-hexane gave pure product

Conditions: temp:135.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a pressure reactor was placed 5-bromo-N-(2,3-dimethoxybenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide (0.1 g, 0.24 mmol), 4-(dimethylamino)benzenethiol (0.147 g, 0.96 mmol) and triethylamine (0.363 g, 0.5 mL, 3.59 mmol). The vessel was purged with nitrogen gas, sealed and heated to 135° C. for 18 hours, after which time it was cooled and the excess triethylamine removed in vacuo. The residue was partitioned between EtOAc/water and extracted. The combined organic extracts were washed with brine, dried over Na2SO4, filtered and the solvent removed. The resulting glass was triturated with diethyl ether and filtered to yield N-(2,3-dimethoxybenzyl)-5-{[4-(dimethylamino)phenyl]thio}-8-hydroxy-1,6-naphthyridine-7-carboxamide as a solid. Into a pressure reactor was placed The vessel was purged with nitrogen gas sealed after which time it was cooled the excess triethylamine removed in vacuo The residue was partitioned between EtOAc/water extracted The combined organic extracts were washed with brine dried over Na2SO4 filtered the solvent removed The resulting glass was triturated with diethyl ether filtered