1,7-二氯-4-氧杂庚烷

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

实验步骤: A mixture of 4-amino-5-chloro-N-[2-(diethylamino)ethyl]-2-hydroxybenzamide hydrochloride (2.50 g, 7.76 mmoles), 2-chloro-ethylmethylether (1.47 g, 15.5 mmoles), potassium carbonate (2.14 g, 15.5 mmoles) and sodium bromide (0.80 g, 7.76 mmoles) in 40 ml of dimethylformamide (DMF) was stirred at reflux for four hours. The DMF was removed under vacuum and the residue was redissolved in methylene chloride and washed with water and dilute NaOH. The solvent was evaporated and the product was chromatographed using a gradient elution of methanol-methylene chloride containing 0.25% NH4OH. The appropriate fractions were combined and evaporated to yield 2.34 g (87.6%) of cream-colored solid. Recrystallization of the residue from ethyl acetate gave the title compound as a white solid, mp 108°-110.5°. The NMR spectrum (90 MHz) in CDCl3 gave the following resonances: δ 8.19 (s, 1H); 6.35 (s, 1H); 4.5 (bs, 2H); 4.2 (m, 2 H); 3.8 (m, 2H); 3.5 (m, 2H); 3.49 (s, 3H); 2.59 (m, 6H); 1.02 (t, 6H). at reflux for four hours The DMF was removed under vacuum the residue was redissolved in methylene chloride washed with water and dilute NaOH The solvent was evaporated the product was chromatographed a gradient elution of methanol-methylene chloride containing 0.25% NH4OH evaporated

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

实验步骤: A mixature of 4-amino-5-chloro-N-[2-(diethylamino)ethyl]-2-hydroxybenzamide hydrochloride (2.50 g, 7.76 mmoles), 2-chloro-ethylmethylether (1.47 g, 15.5 mmoles), potassium carbonate (2.14 g, 15.5 mmoles) and sodium bromide (0.80 g, 7.76 mmoles) in 40 ml of dimethylformamide (DMF) was stirred at reflux for four hours. The DMF was removed under vacuum and the residue was redissolved in methylene chloride and washed with water and dilute NaOH. The solvent was evaporated and the product was chromatographed using a gradient elution of methanol-methylene chloride containing 0.25% NH4OH. The appropriate fractions were combined and evaporated to yield 2.34 g (87.6%) of cream-colored solid. Recrystallization of the residue from ethyl acetate gave the title compound as a white solid, mp 108°-110.5°. The NMR spectrum (90 MHz) in CDCl3 gave the following resonances: δ 8.19 (s, 1H); 6.35 (s, 1H); 4.5 (bs, 2H); 4.2 (m, 2H); 3.8 (m, 2H); 3.5 (m, 2H); 3.49 (s, 3H); 2.59 (m, 6H); 1.02 (t, 6H). at reflux for four hours The DMF was removed under vacuum the residue was redissolved in methylene chloride washed with water and dilute NaOH The solvent was evaporated the product was chromatographed a gradient elution of methanol-methylene chloride containing 0.25% NH4OH evaporated

实验步骤: 投料: 2026-03-25 11：20 取反应瓶，将SM1（36.5mg 0.3mmol 1.0eq），NaOH加入瓶中，随后加入MeOH超声均匀后，随后加入SM2（102.6mg 0.6mmol 2.0eq），保持室温继续反应。\n监测: 2026-03-25 13：30 LC-MS：144748-1-4-R，监测到产物信号，原料还有剩余。 2026-03-25 17：20 LC-MS：144748-1-4-5h，监测到产物信号，原料基本反应完全。\n纯化: 2026-03-26 10：00 旋干反应液，过反相柱进行纯化分离，以水，乙腈作为洗脱剂（200nm，210nm），通过LC-MS对纯化产物进行监测，当洗脱梯度为5%时，出峰P1；当洗脱梯度为25%时，出峰P2；各峰送检LC-MS，发现P2为目标产物峰，将P2旋干后送检核磁（144748-1-t）以及P2与标样混合样（144748-H），与证书对照，基本一致，故后续据此放大。

实验步骤: 投料: 2026-04-08 09：40 取250ml单口瓶，将SM1（2.36g 19.5mmol 1.0eq），NaOH（1.17g 29.2mmol 1.5eq）加入瓶中，随后加入MeOH（60ml）超声均匀后（反应液呈无色透明，底部有白色固体，为SM1和NaOH），随后迅速加入SM2（5g 29.2mmol 1.5eq），保持室温反应。重复投料三次。观察到随着反应的进行，反应液底部的固体逐渐溶解，反应液仍呈无色透明，每隔1小时送LC-MS监测反应进程。\n监测: 2026-04-08 10：50 LC-MS：144748-4-1h，监测到产物信号，原料还有较多剩余。 2026-04-08 12：06 LC-MS：144748-4-2.5h，监测到产物信号，原料还有较多剩余。 2026-04-08 13：35 LC-MS：144748-4-4h，监测到产物信号，原料还有较少剩余。 2026-04-08 15：27 LC-MS：144748-4-6h，监测到产物信号，原料还有少量剩余。 2026-04-08 17：00 LC-MS：144748-4-7.5h，监测到产物信号，主峰为产物峰，原料还有少量剩余，停止反应。\n纯化: 2026-04-09 09：30 对滤液过反相柱进行纯化分离，以水，乙腈作为洗脱剂（200nm，210nm），通过LC-MS对纯化产物进行监测，当洗脱梯度为5%时，出杂质峰P1；当洗脱梯度为35%时，出目标产物峰P2；各峰送检LC-MS，P2为目标产物，收集P2冻干，得到类白色固体1.96g，送检三谱和定量均合格。 2026-04-14 15：30 与第一批合并冻干，重新送检三谱和定量合格，最终入库3.25g，性状为类白色固体。\n后处理: 2026-04-09 09：30 用稀盐酸调节反应液的PH至中性，随后旋干反应液，过反相柱进行纯化分离。加水和乙腈进行溶解，观察到反应液分层，随后过滤反应液，送检LC-MS（144748-LY；144748-GT），发现产物大部分在滤液中，滤饼有少量产物及接两个的产物。

实验步骤: 投料: 2026-04-01 16：00 取250ml单口瓶，将SM1（1.77g 14.6mmol 1.0eq），NaOH（1.17g 29.2mmol 2.0eq）加入瓶中，随后加入MeOH（60ml）超声均匀后，随后迅速加入SM2（5g 29.2mmol 2.0eq），保持室温继续反应。\n监测: 2026-04-01 17：10 LC-MS：144748-3-1h，监测到产物信号，但产物峰较低，让其室温搅拌过夜。 2026-04-02 09：05 LC-MS：144748-3-R，监测到产物信号，原料基本完全反应。\n纯化: 2026-04-02 13：30 用稀盐酸调节反应液的PH至中性，随后常温旋干反应液，后过反相柱进行纯化分离，以水，乙腈作为洗脱剂（200nm，210nm），通过LC-MS对纯化产物进行监测，当洗脱梯度为5%时，出杂质峰P1；当洗脱梯度为35%时，出目标产物峰P2；各峰送检LC-MS，收集P2冻干，得到类白色固体1.3g。

实验步骤: 投料: 2026-04-01 10：20 取反应瓶，将SM1（35.4mg 1.0eq），NaOH（23.4mg 1.5eq）加入瓶中，随后加入MeOH超声均匀后，随后加入SM2（100mg 1.5eq），保持室温继续反应。每隔一小时通过LC-M监测反应进程。\n监测: 2026-04-01 11：20 LC-MS：144748-2-1h，监测到产物信号，原料还有剩余。 2026-04-01 13：30 LC-MS：144748-2-3h，观察到反应效果较SM2（2.0eq）差，随后按2.0eq进行放大。

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

实验步骤: A mixture of 4-amino-5-chloro-N-[2-(diethylamino)ethyl]-2-hydroxybenzamide hydrochloride (2.50 g, 7.76 mmoles), 2-chloro-ethylmethylether (1.47 g, 15.5 mmoles), potassium carbonate (2.14 g, 15.5 mmoles) and sodium bromide (0.80 g, 7.76 mmoles) in 40 ml of dimethylformamide (DMF) was stirred at reflux for four hours. The DMF was removed under vacuum and the residue was redissolved in methylene chloride and washed with water and dilute NaOH. The solvent was evaporated and the product was chromatographed using a gradient elution of methanol-methylene chloride containing 0.25% NH4OH. The appropriate fractions were combined and evaporated to yield 2.34 g (87.6%) of cream-colored solid. Recrystallization of the residue from ethyl acetate gave the title compound as a white solid, mp 108°-110.5°. The NMR spectrum (90MHz) in CDCl3 gave the following resonances: δ 8.19 (s, 1H); 6.35 (s, 1H); 4.5 (bs, 2H); 4.2 (m, 2H); 3.8 (m, 2H); 3.5 (m, 2H); 3.49 (s, 3H); 2.59 (m, 6H); 1.02 (t, 6H). at reflux for four hours The DMF was removed under vacuum the residue was redissolved in methylene chloride washed with water and dilute NaOH The solvent was evaporated the product was chromatographed a gradient elution of methanol-methylene chloride containing 0.25% NH4OH evaporated

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

实验步骤: A mixture of 4-amino-5-chloro-N-[2-(diethylamino)ethyl]-2-hydroxybenzamide hydrochloride (2.50 g, 7.76 mmoles), 2-chloro-ethylmethylether (1.47 g, 15.5 mmoles), potassium carbonate (2.14 g, 15.5 mmoles) and sodium bromide (0.80 g, 7.76 mmoles) in 40 ml of dimethylformamide (DMF) was stirred at reflux for four hours. The DMF was removed under vacuum and the residue was redissolved in methylene chloride and washed with water and dilute NaOH. The solvent was evaporated and the product was chromatographed using a gradient elution of methanol-methylene chloride containing 0.25% NH4OH. The appropriate fractions were combined and evaporated to yield 2.34 g (87.6%) of cream-colored solid. Recrystallization of the residue from ethyl acetate gave the title compound as a white solid, mp 108°-110.5°. The NMR spectrum (90 MHz) in CDCl3 gave the following resonances: δ 8.19 (s, 1H); 6.35 (s, 1H); 4.5 (bs, 2H); 4.2 (m, 2 H); 3.8 (m, 2H); 3.5 (m, 2H); 3.49 (s, 3H); 2.59 (m, 6H); 1.02 (t, 6H). at reflux for four hours The DMF was removed under vacuum the residue was redissolved in methylene chloride washed with water and dilute NaOH The solvent was evaporated the product was chromatographed a gradient elution of methanol-methylene chloride containing 0.25% NH4OH evaporated

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

实验步骤: A mixature of 4-amino-5-chloro-N-[2-(diethylamino)ethyl]-2-hydroxybenzamide hydrochloride (2.50 g, 7.76 mmoles), 2-chloro-ethylmethylether (1.47 g, 15.5 mmoles), potassium carbonate (2.14 g, 15.5 mmoles) and sodium bromide (0.80 g, 7.76 mmoles) in 40 ml of dimethylformamide (DMF) was stirred at reflux for four hours. The DMF was removed under vacuum and the residue was redissolved in methylene chloride and washed with water and dilute NaOH. The solvent was evaporated and the product was chromatographed using a gradient elution of methanol-methylene chloride containing 0.25% NH4OH. The appropriate fractions were combined and evaporated to yield 2.34 g (87.6%) of cream-colored solid. Recrystallization of the residue from ethyl acetate gave the title compound as a white solid, mp 108°-110.5°. The NMR spectrum (90 MHz) in CDCl3 gave the following resonances: δ 8.19 (s, 1H); 6.35 (s, 1H); 4.5 (bs, 2H); 4.2 (m, 2H); 3.8 (m, 2H); 3.5 (m, 2H); 3.49 (s, 3H); 2.59 (m, 6H); 1.02 (t, 6H). at reflux for four hours The DMF was removed under vacuum the residue was redissolved in methylene chloride washed with water and dilute NaOH The solvent was evaporated the product was chromatographed a gradient elution of methanol-methylene chloride containing 0.25% NH4OH evaporated