2,2-二甲基-1,3-二氧戊环-4-甲醛

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: A mixture of 3-(1-methylindol-3-yl)-4-(3-aminophenyl)-1H-pyrrole-2,5-dione (100 mg, 0.32 mmol) and 2,2-dimethyldioxolane-4-carboxaldehyde (0.38 mmol) (prepared as described in Kumont, von R., et al. Helv. Chim. Acta., 66, 814, (1983)) in dichloromethane (12 mL) was stirred at room temperature for 10 min., and then Na(OAc)3BH (120 mg, 0.57 mmol) was added. The reaction mixture was stirred overnight and then partition between EtOAc and H20. The organic layer was separated, washed with water and concentrated. The crude product was purified by preparatory TLC with 3/1 hexanes/EtOAc to give 3-(1-methylindol-3-yl)-4-[3-(2,2-dimethyldioxolan-4-ylmethylamino)phenyl]-1H-pyrrole-2,5-dione (32.6 mg, 24%). The reaction mixture was stirred overnight partition between EtOAc and H20 The organic layer was separated washed with water concentrated The crude product was purified by preparatory TLC with 3/1 hexanes/EtOAc

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

实验步骤: To a solution of propylamine (0.72 mL, 7.7 mmol) and 2,2-dimethyl-1,3-dioxolane-4-carbaldehyde (1.0 g, 7.7 mmol) in 1,2-dichloroethane (25 mL) was added sodium triacetoxyborohydride (2.28 g, 10.8 mmol). The mixture was stirred for 1.5 h at room temperature. The reaction mixture was then quenched with sat'd aq NaHCO3 and extracted with EtOAc. The organic layer was dried with MgSO4, filtered, and concentrated under reduced pressure to give the crude material that was purified by silica gel flash column chromatography (CH2Cl2 to 10% MeOH in CH2Cl2, gradient) to afford 1.26 g (73%) of N-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)propan-1-amine. The reaction mixture was then quenched with sat'd aq NaHCO3 extracted with EtOAc The organic layer was dried with MgSO4 filtered concentrated under reduced pressure to give the crude material that was purified by silica gel flash column chromatography (CH2Cl2 to 10% MeOH in CH2Cl2, gradient)

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

实验步骤: To a solution of propylamine (0.72 mL, 7.7 mmol) and 2,2-dimethyl-1,3-dioxolane-4-carbaldehyde (1.0 g, 7.7 mmol) in 1,2-dichloroethane (25 mL) was added sodium triacetoxyborohydride (2.28 g, 10.8 mmol). The mixture was stirred for 1.5 h at room temperature. The reaction mixture was then quenched with sat'd aq NaHCO3 and extracted with EtOAc. The organic layer was dried with MgSO4, filtered, and concentrated under reduced pressure to give the crude material that was purified by silica gel flash column chromatography (CH2Cl2 to 10% MeOH in CH2Cl2, gradient) to afford 1.26 g (73%) of N-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)propan-1-amine. The reaction mixture was then quenched with sat'd aq NaHCO3 extracted with EtOAc The organic layer was dried with MgSO4 filtered concentrated under reduced pressure to give the crude material that was purified by silica gel flash column chromatography (CH2Cl2 to 10% MeOH in CH2Cl2, gradient)

反应条件: temp:-60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of anhydrous DMSO (3.41 mL, 48 mmol) in CH2Cl2 (5 mL) was added dropwise to a stirred solution of oxalyl chloride (1.92 mL, 22 mmol) in CH2Cl2 (50 mL) at −60° C. To this mixture was added a solution of (2,2-dimethyl-[1,3]dioxolan-4-yl)-methanol (2.48 mL, 20 mmol) in CH2Cl2 (10 mL). The resulting mixture was stirred for 15 min at −60° C. TEA (13.9 mL, 100 mmol) was added dropwise. The reaction mixture was then warmed to room temperature. Water (50 mL) and CH2Cl2 (50 mL) were added. The organic layer was separated and washed with water (25 mL). The aqueous layer was extracted with CH2Cl2 (3×50 mL). The organic layers were dried over MgSO4, filtered, and concentrated under reduced pressure to afford the crude 2,2-dimethyl-1,3-dioxolane-4-carbaldehyde that was used directly without further purification. The reaction mixture was then warmed to room temperature The organic layer was separated washed with water (25 mL) The aqueous layer was extracted with CH2Cl2 (3×50 mL) The organic layers were dried over MgSO4 filtered concentrated under reduced pressure

反应条件: temp:-60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of anhydrous DMSO (3.41 mL, 48 mmol) in CH2Cl2 (5 mL) was added dropwise to a stirred solution of oxalyl chloride (1.92 mL, 22 mmol) in CH2Cl2 (50 mL) at −60° C. To this mixture was added a solution of (2,2-dimethyl-[1,3]dioxolan-4-yl)-methanol (2.48 mL, 20 mmol) in CH2Cl2 (10 mL). The resulting mixture was stirred for 15 min at −60° C. TEA (13.9 mL, 100 mmol) was added dropwise. The reaction mixture was then warmed to room temperature. Water (50 mL) and CH2Cl2 (50 mL) were added. The organic layer was separated and washed with water (25 mL). The aqueous layer was extracted with CH2Cl2 (3×50 mL). The organic layers were dried over MgSO4, filtered, and concentrated under reduced pressure to afford the crude 2,2-dimethyl-1,3-dioxolane-4-carbaldehyde that was used directly without further purification. The reaction mixture was then warmed to room temperature The organic layer was separated washed with water (25 mL) The aqueous layer was extracted with CH2Cl2 (3×50 mL) The organic layers were dried over MgSO4 filtered concentrated under reduced pressure

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

实验步骤: To a solution of propylamine (0.72 mL, 7.7 mmol) and 2,2-dimethyl-1,3-dioxolane-4-carbaldehyde (1.0 g, 7.7 mmol) in 1,2-dichloroethane (25 mL) was added sodium triacetoxyborohydride (2.28 g, 10.8 mmol). The mixture was stirred for 1.5 h at room temperature. The reaction mixture was then quenched with sat'd aq NaHCO3 and extracted with EtOAc. The organic layer was dried with MgSO4, filtered, and concentrated under reduced pressure to give the crude material that was purified by silica gel flash column chromatography (CH2Cl2 to 10% MeOH in CH2Cl2, gradient) to afford 1.26 g (73%) of N-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)propan-1-amine. The reaction mixture was then quenched with sat'd aq NaHCO3 extracted with EtOAc The organic layer was dried with MgSO4 filtered concentrated under reduced pressure to give the crude material that was purified by silica gel flash column chromatography (CH2Cl2 to 10% MeOH in CH2Cl2, gradient)

反应条件: temp:-60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of anhydrous DMSO (3.41 mL, 48 mmol) in CH2Cl2 (5 mL) was added dropwise to a stirred solution of oxalyl chloride (1.92 mL, 22 mmol) in CH2Cl2 (50 mL) at −60° C. To this mixture was added a solution of (2,2-dimethyl-[1,3]dioxolan-4-yl)-methanol (2.48 mL, 20 mmol) in CH2Cl2 (10 mL). The resulting mixture was stirred for 15 min at −60° C. TEA (13.9 mL, 100 mmol) was added dropwise. The reaction mixture was then warmed to room temperature. Water (50 mL) and CH2Cl2 (50 mL) were added. The organic layer was separated and washed with water (25 mL). The aqueous layer was extracted with CH2Cl2 (3×50 mL). The organic layers were dried over MgSO4, filtered, and concentrated under reduced pressure to afford the crude 2,2-dimethyl-1,3-dioxolane-4-carbaldehyde that was used directly without further purification. The reaction mixture was then warmed to room temperature The organic layer was separated washed with water (25 mL) The aqueous layer was extracted with CH2Cl2 (3×50 mL) The organic layers were dried over MgSO4 filtered concentrated under reduced pressure

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

实验步骤: To a solution of propylamine (0.72 mL, 7.7 mmol) and 2,2-dimethyl-1,3-dioxolane-4-carbaldehyde (1.0 g, 7.7 mmol) in 1,2-dichloroethane (25 mL) was added sodium triacetoxyborohydride (2.28 g, 10.8 mmol). The mixture was stirred for 1.5 h at room temperature. The reaction mixture was then quenched with sat'd aq NaHCO3 and extracted with EtOAc. The organic layer was dried with MgSO4, filtered, and concentrated under reduced pressure to give the crude material that was purified by silica gel flash column chromatography (CH2Cl2 to 10% MeOH in CH2Cl2, gradient) to afford 1.26 g (73%) of N-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)propan-1-amine. The reaction mixture was then quenched with sat'd aq NaHCO3 extracted with EtOAc The organic layer was dried with MgSO4 filtered concentrated under reduced pressure to give the crude material that was purified by silica gel flash column chromatography (CH2Cl2 to 10% MeOH in CH2Cl2, gradient)

反应条件: temp:-60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of anhydrous DMSO (3.41 mL, 48 mmol) in CH2Cl2 (5 mL) was added dropwise to a stirred solution of oxalyl chloride (1.92 mL, 22 mmol) in CH2Cl2 (50 mL) at −60° C. To this mixture was added a solution of (2,2-dimethyl-[1,3]dioxolan-4-yl)-methanol (2.48 mL, 20 mmol) in CH2Cl2 (10 mL). The resulting mixture was stirred for 15 min at −60° C. TEA (13.9 mL, 100 mmol) was added dropwise. The reaction mixture was then warmed to room temperature. Water (50 mL) and CH2Cl2 (50 mL) were added. The organic layer was separated and washed with water (25 mL). The aqueous layer was extracted with CH2Cl2 (3×50 mL). The organic layers were dried over MgSO4, filtered, and concentrated under reduced pressure to afford the crude 2,2-dimethyl-1,3-dioxolane-4-carbaldehyde that was used directly without further purification. The reaction mixture was then warmed to room temperature The organic layer was separated washed with water (25 mL) The aqueous layer was extracted with CH2Cl2 (3×50 mL) The organic layers were dried over MgSO4 filtered concentrated under reduced pressure

实验步骤: 投料: 第一瓶：取SM1（42g 1eq）于瓶中。加入600mlTHF溶解，在冰浴下加入；磷酰基乙酸三乙酯（108g 1.5eq），碳酸钾（356g 8eq）（溶于600ml水中），常温搅拌过夜 第一瓶：取SM1（42g 1eq）于瓶中。加入600mlTHF溶解，在冰浴下加入；磷酰基乙酸三原子（108g 1.5eq），碳酸钾（356g 8eq）（溶于600ml水中），常温搅拌过夜 送检GCMS（131246-1-1-GY）（131246-1-2-GY），原料已反应完全，TLC点板（PE：EA=5:1）出现产物点，停止反应 加入水和EA萃取反应液，收集有机相，无水硫酸钠干燥，旋干得到M-C4X-131246-TM1粗品。 将粗品直接湿法上样过硅胶柱，洗脱梯度为PE，在PE时冲出产物，送就按GCMS，里面含有部分磷酰基乙酸三乙酯，直接用于下一步。

实验步骤: 投料: 取SM1（13g 1eq）于1L单口瓶中，加入250mlTHF溶解后，在冰浴下加入磷酰基乙酸三乙酯（32ml 1.5eq），碳酸钾（110g 8eq）（溶于250ml水中），转至常温反应过夜 送检GCMS（131246-1-x-GY)，有产物信号生成，TLC点板（PE：EA=5:1）有新的紫外点产生。 加入EA和水萃取反应液，反复萃取水相三次至TLC点板无紫外，收集有机相，无水硫酸钠干燥后，旋掉大部分溶剂，加入硅胶粉拌样过正相柱 洗脱梯度为PE、PE：EA=20:1、PE：EA=10:1，在PE：EA=10:1时冲出紫外点，送检GCMS，确认为目标产物，收集浓缩，得到8.1gM-C4X-131246-TM1