3-羟基-N-甲基苯胺

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To 3-(N-methylamino)phenol (10 g, 80 mmol), dissolved in 80 ml of NMP, was added allyl bromide (9.8 ml, 113 mmol) via syringe. The yellow solution was heated to 80° C. for 4 hours. The reaction mixture was poured into distilled water (200 ml) and saturated aqueous sodium bicarbonate solution was added. Extraction with diethyl ether (3×200 ml), drying over anhydrous magnesium sulfate, filtration and concentration vacuo yielded 18.0 g of 3-(N-allyl-N-methylamino)phenol as a viscous green tinted oil. Vacuum distillation at 1 torr (110°-120° C.) yielded 10.5 g (80%) as a pale yellow oil. The reaction mixture was poured into distilled water (200 ml) and saturated aqueous sodium bicarbonate solution was added Extraction with diethyl ether (3×200 ml) drying over anhydrous magnesium sulfate, filtration and concentration vacuo

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To 3-(N-methylamino)phenol (10 g, 80 mmol), dissolved in 80 ml of NMP, was added allyl bromide (9.8 ml, 113 mmol) via syringe. The yellow solution was heated to 80° C. for 4 hours. The reaction mixture was poured into distilled water (200 ml) and saturated aqueous sodium bicarbonate solution was added. Extraction with diethyl ether (3×200 ml), drying over anhydrous magnesium sulfate, filtration and concentration vacuo yielded 18.0 g of 3-(N-allyl-N-methylamino)phenol as a viscous green tinted oil. Vacuum distillation at 1 torr (110°-120° C.) yielded 10.5 g (80%) as a pale yellow oil. The reaction mixture was poured into distilled water (200 ml) and saturated aqueous sodium bicarbonate solution was added Extraction with diethyl ether (3×200 ml) drying over anhydrous magnesium sulfate, filtration and concentration vacuo

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

实验步骤: This compound was obtained (yield 45%) based on the method described in Production Example 2B using 4,6-dichloro-2-methylpyrimidine instead of the 4,6-dichloro-2-ethylpyrimidine, and using 3-methylaminophenol instead of the 3-aminophenol. This compound was obtained (yield 45%)

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

实验步骤: This compound was obtained (yield 45%) based on the method described in Production Example 2B using 4,6-dichloro-2-methylpyrimidine instead of the 4,6-dichloro-2-ethylpyrimidine, and using 3-methylaminophenol instead of the 3-aminophenol. This compound was obtained (yield 45%)

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

实验步骤: This compound was obtained (yield 43%) based on the method described in Production Example 2B using 4,6-dichloropyrimidine instead of the 4,6-dichloro-2-ethylpyrimidine, and using 3-methylaminophenol instead of the 3-aminophenol. This compound was obtained (yield 43%)

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To 3- (N-methylamino) phenol (10 g, 80 mmol) , dissolved in 80 ml of NMP, was added allyl bromide (9.8 ml, 113 mmol) via syringe. The yellow solution was heated to 80° C. for 4 hours. The reaction mixture was poured into distilled water (200 ml) and saturated aqueous sodium bicarbonate solution was added. Extraction with diethyl ether (3×200 ml), drying over anhydrous magnesium sulfate, filtration and concentration in vacuo yielded 18.0 g of 3-(N-allyl-N-methylamino)phenol as a viscous green tinted oil. Vacuum distillation at 1 torr (110°-120° C.) yielded 10.5 g (80%) as a pale yellow oil. The reaction mixture was poured into distilled water (200 ml) and saturated aqueous sodium bicarbonate solution was added Extraction with diethyl ether (3×200 ml) drying over anhydrous magnesium sulfate, filtration and concentration in vacuo

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To 3- (N-methylamino) phenol (10 g, 80 mmol) , dissolved in 80 ml of NMP, was added allyl bromide (9.8 ml, 113 mmol) via syringe. The yellow solution was heated to 80° C. for 4 hours. The reaction mixture was poured into distilled water (200 ml) and saturated aqueous sodium bicarbonate solution was added. Extraction with diethyl ether (3×200 ml), drying over anhydrous magnesium sulfate, filtration and concentration in vacuo yielded 18.0 g of 3-(N-allyl-N-methylamino)phenol as a viscous green tinted oil. Vacuum distillation at 1 torr (110°-120° C.) yielded 10.5 g (80%) as a pale yellow oil. The reaction mixture was poured into distilled water (200 ml) and saturated aqueous sodium bicarbonate solution was added Extraction with diethyl ether (3×200 ml) drying over anhydrous magnesium sulfate, filtration and concentration in vacuo

实验步骤: 投料: 取250ml单口瓶，依次加入SM1，THF溶解，冰浴下加入钠氢，搅拌30min，再加入SM2，加毕转移至60℃加热过夜。\n监测: LCMS（CP129635-2-2）显示反应完全，体系干净，主峰为产物峰（M+=266），TLC原料消失，有一个极性变大的新点（D:M=20：1）。\n后处理: 将反应冷却至室温，置于冰浴，缓慢滴加纯水淬灭反应至体系不冒泡，待体系稳定后加入100ml水和EA萃取三次，合并EA相，干燥浓缩得产物粗品。\n纯化: 硅胶柱层析，DCM和甲醇作流动相，纯DCM出杂质和产物交叉，慢慢升高甲醇比例至2%, 部分产物为纯品，收集浓缩得产物纯品棕色油状物1.7g。\n纯化: 由于产物一直是油状物，并且核磁2.7位置多了一组峰，怀疑为原料杂质，将之前没过纯的产物和纯的产物混合，硅胶柱层析，PE和EA作流动相，60%EA到100%EA出纯产物，收集浓缩得产物纯品棕色油状物6g。\n纯化: 由于产物还是油状物，并且核磁2.7位置多了一组峰，反相纯化，乙腈和水作流动相，30%乙腈有一组200nm吸收的杂质峰，40%乙腈出产物，收集浓缩得产物纯品米黄色油状物5g。产品常温放置两天后凝固成固体，捣碎成粉末，送检，HNMR, LCMS，HPLC，QHNMR表征合格，入库4.88g米黄色固体。

实验步骤: 纯化: 硅胶柱层析，PE:EA=35%出产物，收集浓缩得产物纯品棕色油状物3.5g。\n投料: 取250ml三口瓶，加入SM1，超干THF，置换N2，冰浴下滴加2.5M的氢化铝锂溶液，滴毕转移至65℃加热过夜。\n后处理: 向体系中缓慢滴加冰水淬灭反应，然后缓慢加入40ml浓盐酸调节PH，调至弱碱性，加入EA萃取三次，合并有机相，干燥浓缩。\n监测: TLC显示反应完全（PE:EA=3:1），原料消失，体系干净，生成一个极性变大的新点。LCMS(CP129635-1-2)显示主峰为产物峰（M+=124）

实验步骤: 投料: 取50ml单口瓶，依次加入SM1，THF溶解，冰浴下加入钠氢，搅拌30min，再加入SM2，加毕转移至60℃加热过夜。\n监测: LCMS（CP129635-2-1）显示反应完全，体系干净，主峰为产物峰（M+=266），TLC原料消失，有一个极性变大的新点（D:M=20：1）。

实验步骤: 投料: 取50ml三口瓶，加入SM1，超干THF，置换N2，冰浴下滴加2.5M的氢化铝锂溶液，滴毕转移至65℃加热过夜。\n监测: TLC显示反应完全（PE:EA=3:1），原料消失，体系干净，生成一个极性变大的新点。LCMS(CP129635-1-1)显示主峰为产物峰（M+=124）\n后处理: 向体系中滴加冰水淬灭反应，然后加入1ml浓盐酸调节PH，加入EA萃取三次，合并有机相，干燥浓缩。\n纯化: 硅胶柱层析，PE:EA=35%出产物，收集浓缩得产物，检测HNMR（CP129635-1-1）显示确证为产物。

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

实验步骤: 3-Aminophenol (5.37 g, 49.2 mmol) in ethylformate (30 mL) was treated with p-toluenesulfonic acid (50 mg) and heated at reflux. After 18 hours, the volatiles were evaporated under reduced pressure. The residue was taken up in ethyl acetate and washed with 1N HCl, saturated NaHCO3, brine, dried (Na2SO4), filtered, and the filtrate concentrated under reduced pressure. The residue was dissolved in THF (25 mL) and treated with 1M borane tetrahydofuran complex (27.2 mL, 27.2 mmol) in THF. After 18 hours at ambient temperature, the mixture was carefully quenched by addition of 1N HCl. After stirring for 30 minutes, the solution was basified and extracted with ethyl acetate. The organic layer was separated, washed with brine, dried (Na2SO4), filtered, and the filtrate concentrated under reduced pressure. The residue was purified by flash chromatography (30% ethyl acetate/hexanes) to provide the title compound as a viscous yellow oil (1.72 g, 28% yield). 1H NMR (300 MHz, CDCl3) δ 7.03 (t, 1H), 6.13-6.24 (m, 2H), 6.11 (t, 1H), 4.54 (bs, 1H), 3.72 (bs, 1H), 2.82 (s, 3H); MS (DCI/NH3) 124 (M+H)+, 141 (M+NH4)+. heated at reflux the volatiles were evaporated under reduced pressure washed with 1N HCl, saturated NaHCO3, brine dried (Na2SO4) filtered the filtrate concentrated under reduced pressure The residue was dissolved in THF (25 mL) After 18 hours at ambient temperature the mixture was carefully quenched by addition of 1N HCl extracted with ethyl acetate The organic layer was separated washed with brine dried (Na2SO4) filtered the filtrate concentrated under reduced pressure The residue was purified by flash chromatography (30% ethyl acetate/hexanes)