2,6-二氯-3-甲氧基苯胺

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 2,4-dichloro-3-aminophenol hydrochloride (GLSynthesis, 7.70 g, 35.9 mmol, 1.0 eq.) in acetone is added powdered potassium hydroxide 85% (9.48 g, 143.6 mmol, 4.0 eq.) in small portions. Then, dimethyl sulfate (5.13 ml, 53.9 mmol, 1.5 eq.) is added at such a rate that the internal temperature does not rise above 30° C. After 1 h stirring at room temperature water (50 ml) is added and stirring is continued for another hour. The solvent is evaporated and the residue is distributed between ethyl acetate (150 ml) and water (100 ml). The organic layer is isolated, dried over Na2SO4 and evaporated to give a yellow oil. Kugelrohr distillation affords the desired product as a colorless oil: b.p. 150° C./0.3 mbar, HPLC: tR=5.61 min (purity: 90%, gradient A), 400 MHz 1H-NMR (CDCl3) δ: 3.87 (s, 3H, OMe), 4.49 (br s, 2H, NH2), 6.30 (d, 1H, Ar—H4), 7.11 (d, 1H, Ar—H5). does not rise above 30° C is added is continued for another hour The solvent is evaporated The organic layer is isolated dried over Na2SO4 evaporated to give a yellow oil Kugelrohr distillation

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 2,4-dichloro-3-aminophenol hydrochloride (GLSynthesis, 7.70 g, 35.9 mmol, 1.0 eq.) in acetone is added powdered potassium hydroxide 85% (9.48 g, 143.6 mmol, 4.0 eq.) in small portions. Then, dimethyl sulfate (5.13 ml, 53.9 mmol, 1.5 eq.) is added at such a rate that the internal temperature does not rise above 30° C. After 1 h stirring at room temperature water (50 ml) is added and stirring is continued for another hour. The solvent is evaporated and the residue is distributed between ethyl acetate (150 ml) and water (100 ml). The organic layer is isolated, dried over Na2SO4 and evaporated to give a yellow oil. Kugelrohr distillation affords the desired product as a colorless oil: b.p. 150° C./0.3 mbar, HPLC: tR=5.61 min (purity: 90%, gradient A), 400 MHz 1H-NMR (CDCl3) δ: 3.87 (s, 3H, OMe), 4.49 (br s, 2H, NH2), 6.30 (d, 1H, Ar—H4), 7.11 (d, 1H, Ar—H5). does not rise above 30° C is added is continued for another hour The solvent is evaporated The organic layer is isolated dried over Na2SO4 evaporated to give a yellow oil Kugelrohr distillation

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 60.7 g of 2,6-dichloro-3-methoxy-aniline are dissolved in 65 ml of toluene and treated with 25 ml of thiophosgene in 50 ml of toluene. The solution obtained is heated to boiling under reflux overnight and subsequently evaporated in vacuo. There is obtained 2,6-dichloro-3-methoxyphenylisothiocyanate of boiling point 99° (0.13 Torr). The solution obtained is heated under reflux overnight subsequently evaporated in vacuo

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 62.4 g of 2,4-dichloro-3-nitroanisole in 750 ml of ethanol is treated with 19 g of Raney-nickel and hydrogenated for 8 hours. The obtained solution is filtered and evaporated in vacuo. The residue is taken up in methylene chloride and the solution is washed with a dilute sodium carbonate solution. After drying the organic phase over sodium sulfate and evaporating in vacuo, there is obtained 2,6-dichloro-3-methoxyaniline of boiling point 84° (0.1 Torr). The obtained solution is filtered evaporated in vacuo the solution is washed with a dilute sodium carbonate solution After drying the organic phase over sodium sulfate evaporating in vacuo

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 2-(2,5-dichloro-phenoxy)-5-fluoro-nicotinoyl chloride (76.6 mg, 0.24 mmol, 1.0 equiv) in anhydrous DMF (1 mL) was added N-ethyldiisopropylamine (155 mg, 205 μL, 1.2 mmol, 5.0 equiv; [CAS RN 7087-68-5]) and 2,6-dichloro-3-methoxy-phenylamine (50.7 mg, 0.264 mmol, 1.1 equiv; [CAS RN 55285-43-3]) and the reaction mixture stirred at rt over night. To this solution was added sodium hydride (20.6 mg, 0.48 mmol, 2.0 equiv; 55% free-flowing powder moistened with oil; [CAS RN 7646-69-7]) and iodomethane (68.2 mg, 29 μL, 0.48 mmol, 2.0 equiv; [CAS RN 74-88-4]) and stirring of the reaction mixture at rt continued for 2 h. Removal of the solvent mixture under reduced pressure and purification by preparative HPLC on reversed phase (Xterra® PrepMSC 18, 5 μm, 19×50 mm column equipped with a Gilson Liquid Handler 215 autosampler, two Rainin Dynamax® SD-300 pumps, a Sedex ELSD 75 lightscatter and a Dionex UVD 340S UV detector) eluting with a gradient of acetonitrile/water provided 8.1 mg (7%) of the title compound as an off-white powder. MS (ISP): 490.9 [M+H]+. stirring of the reaction mixture at rt Removal of the solvent mixture under reduced pressure and purification by preparative HPLC on reversed phase (Xterra® PrepMSC 18, 5 μm, 19×50 mm column equipped with a Gilson Liquid Handler 215 autosampler, two Rainin Dynamax® SD-300 pumps a Sedex ELSD 75 lightscatter and a Dionex UVD 340S UV detector) eluting with a gradient of acetonitrile/water

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 2-fluoro-5-(3-fluorophenyl)benzoic acid (intermediate III(a)) (1.6 g, 7 mmol, 3.0 eq) in SOCl2 (20 mL) was heated at reflux for 3 h. The excess thionyl chloride was removed in vacuo and the residue obtained dissolved in THF (10 mL) and added dropwise to a solution of 2,6-dichloro-3-methoxy-aniline (450 mg, 2.3 mmol, 1.0 eq) and NaH (85 mg, 3.4 mmol, 1.5 eq) in THF (10 mL). The reaction was stirred at room temperature for 2 h then quenched by addition of aqueous NH4Cl. The mixture was extracted with EtOAc and the combined organic extracts were dried (Na2SO4), filtered and evaporated in vacuo. The residue obtained was purified by column chromatography (EtOAc:petroleum ether, 0:1 to 1:4) to give the title compound (200 mg, 21%). at reflux for 3 h The excess thionyl chloride was removed in vacuo the residue obtained then quenched by addition of aqueous NH4Cl The mixture was extracted with EtOAc the combined organic extracts were dried (Na2SO4) filtered evaporated in vacuo The residue obtained was purified by column chromatography (EtOAc:petroleum ether, 0:1 to 1:4)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 1,3-dichloro-4-methoxy-2-nitro-benzene (550 mg, 2.5 mmol, 1.0 eq) in EtOAc (20 mL) was added Pd/C (10% Pd, 50 mg) and the reaction was stirred under a hydrogen atmosphere overnight. The catalyst was removed by filtration and the filtrate was evaporated in vacuo to give the title compound (500 mg, 100%). The catalyst was removed by filtration the filtrate was evaporated in vacuo

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 2,4-dichloro-3-aminophenol hydrochloride (GLSynthesis, 7.70 g, 35.9 mmol, 1.0 eq.) in acetone is added powdered potassium hydroxide 85% (9.48 g, 143.6 mmol, 4.0 eq.) in small portions. Then, dimethyl sulfate (5.13 ml, 53.9 mmol, 1.5 eq.) is added at such a rate that the internal temperature does not rise above 30° C. After 1 h stirring at room temperature water (50 ml) is added and stirring is continued for another hour. The solvent is evaporated and the residue is distributed between ethyl acetate (150 ml) and water (100 ml). The organic layer is isolated, dried over Na2SO4 and evaporated to give a yellow oil. Kugelrohr distillation affords the desired product as a colorless oil: b.p. 150° C./0.3 mbar, HPLC: tR=5.61 min (purity: 90%, gradient A), 400 MHz 1H-NMR (CDCl3) δ: 3.87 (s, 3H, OMe), 4.49 (br s, 2H, NH2), 6.30 (d, 1H, Ar—H4), 7.11 (d, 1H, Ar—H5). does not rise above 30° C is added is continued for another hour The solvent is evaporated The organic layer is isolated dried over Na2SO4 evaporated to give a yellow oil Kugelrohr distillation