叔-丁基1,2,3,4,4a,5,7,7a-八氢吡咯[3,4-b]吡啶-6-羧酸盐

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 tert-butyl hexahydro-1H-pyrrolo[3,4-b]pyridine-6(2H)-carboxylate (1.60 g), 1-bromo-3-chloropropane (1.50 mL) and K2CO3 (3.00 g) in acetone was heated to reflux for 9 h. The reaction mixture was cooled to rt and filtered. The filtrate was concentrated in vacuo and the residue was chromatographed with a silica gel column (eluting agent: 1:1 (v/v) PE/EA) to give the title compound as yellow oil (0.53 g, 65.00%), HPLC: 89.00%. The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 303.2 (M+1). was heated to reflux for 9 h filtered The filtrate was concentrated in vacuo the residue was chromatographed with a silica gel column (eluting agent: 1:1 (v/v) PE/EA)

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

实验步骤: A mixture of tert-butyl hexahydro-1H-pyrrolo[3,4-b]pyridine-6(2H)-carboxylate (1.60 g), 1-bromo-3-chloropropane (1.50 mL) and K2CO3 (3.00 g) in acetone was heated to reflux for 9 h. The reaction mixture was cooled to rt and filtered. The filtrate was concentrated in vacuo and the residue was chromatographed with a silica gel column (eluting agent: 1:1 (v/v) PE/EA) to give the title compound as yellow oil (0.53 g, 65.00%), HPLC: 89.00%. The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 303.2 (M+1). was heated to reflux for 9 h filtered The filtrate was concentrated in vacuo the residue was chromatographed with a silica gel column (eluting agent: 1:1 (v/v) PE/EA)

反应条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of tert-butyl 5H-pyrrolo[3,4-b]pyridine-6(7H)-carboxylate (1.50 g) in glycol monomethyl ether was added a catalytic amount of 10% Pd/C. The suspension was heated to 70° C. and stirred for 6 h under H2. The resulted mixture was cooled to rt, poured into 100 mL of water and extracted with CH2Cl2 (50 mL×3). The combined organic phases were dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated in vacuo to give the title compound as pale yellow oil (0.95 g, 65.00%). The crude product was used for the next step without further purification. The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 227.2 (M+1). The resulted mixture was cooled to rt extracted with CH2Cl2 (50 mL×3) The combined organic phases were dried over anhydrous Na2SO4 filtered The filtrate was concentrated in vacuo

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

实验步骤: The title compound was prepared following the same general protocol as described for rac-((2S,3S)-2-(aminomethyl)-3-methylpiperidin-1-yl)(5-(4-fluorophenyl)-2-methylthiazol-4-yl)methanone in Example A65 using tert-butyl hexahydro-1H-pyrrolo[3,4-b]pyridine-6(2H)-carboxylate. MS (ESI) 346 (M+H).

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

实验步骤: The title compound was prepared following the same general protocol as described for rac-((2S,3S)-2-(aminomethyl)-3-methylpiperidin-1-yl)(5-(4-fluorophenyl)-2-methylthiazol-4-yl)methanone in Example A65 using tert-butyl hexahydro-1H-pyrrolo[3,4-b]pyridine-6(2H)-carboxylate. MS (ESI) 346 (M+H).

实验步骤: 投料: 0-21 14:11: 反应过程： 将(4aS,7aS)-octahydro-1H-pyrrolo[3,4-b]pyridine、DCM投入500 ml三口瓶中，搅拌冰水浴降温至10℃以下，控温10℃以下滴加Boc酸的DCM溶液，滴加结束后在室温下反应2.5 h。TLC检测(展开剂:DCM/MeOH= 20/1，产品的Rf =0.3，I2显色)反应完毕。 3）纯化： 往体系加入50 ml水，加入60 ml二氯甲烷萃取，重复操作两次，合并上述有机相，用饱和食盐水洗涤，无水硫酸钠干燥，过滤，滤液真空浓缩得到粗品. 柱层析纯化(200-300目硅胶)，湿法装柱、湿法上样，以DCM/MeOH=50/1 -DCM/MeOH = 20/1洗脱得到产品，浓缩得类白色固体tert-butyl (4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridine-6-carboxylate。

实验步骤: 投料: 反应过程： 将tert-butyl (4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridine-6-carboxylate、NaHCO3、H2O、THF、I2投入500 ml三口瓶中，搅拌升温至50 ℃搅拌反应3 h。有机相送LC-MS确认无原料剩余。 3）纯化： 将反应液倒入质量分数为20%硫代硫酸钠水溶液和饱和碳酸氢钠水溶液的混合溶剂的冰水浴中搅拌，用DCM萃取，重复萃取操作两次，合并有机相用饱和氯化钠水溶液洗涤、无水硫酸钠干燥，有机相浓缩至恒重得到棕色固体tert-butyl (4aS,7aS)-2-oxooctahydro-6H-pyrrolo[3,4-b]pyridine-6-carboxylate （收率:83.3%)。

实验步骤: 投料: 反应过程： 将(4aS,7aS)-octahydro-1H-pyrrolo[3,4-b]pyridine、DCM投入500 ml三口瓶中，搅拌冰水浴降温至10℃以下，控温10℃以下滴加Boc酸的DCM溶液，滴加结束后在室温下反应2.5 h。TLC检测(展开剂:DCM/MeOH= 20/1，产品的Rf =0.3，I2显色)反应完毕。 3）纯化： 往体系加入50 ml水，加入60 ml二氯甲烷萃取，重复操作两次，合并上述有机相，用饱和食盐水洗涤，无水硫酸钠干燥，过滤，滤液真空浓缩得到粗品. 柱层析纯化(200-300目硅胶)，湿法装柱、湿法上样，以DCM/MeOH=50/1 -DCM/MeOH = 20/1洗脱得到产品，浓缩得类白色固体tert-butyl (4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridine-6-carboxylate。

实验步骤: 投料: 06-15 09:35: 2）反应过程： 将tert-butyl (4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridine-6-carboxylate、NaHCO3、H2O、THF、I2投入500 ml三口瓶中，搅拌升温至50 ℃搅拌反应3 h。有机相送LC-MS确认无原料剩余。 3）纯化： 将反应液倒入质量分数为20%硫代硫酸钠水溶液和饱和碳酸氢钠水溶液的混合溶剂的冰水浴中搅拌，用DCM萃取，重复萃取操作两次，合并有机相用饱和氯化钠水溶液洗涤、无水硫酸钠干燥，有机相浓缩至恒重得到棕色固体tert-butyl (4aS,7aS)-2-oxooctahydro-6H-pyrrolo[3,4-b]pyridine-6-carboxylate （收率:83.3%)。

实验步骤: 投料: 06-13 09:29: 2）反应过程： 将(4aS,7aS)-octahydro-1H-pyrrolo[3,4-b]pyridine、DCM投入500 ml三口瓶中，搅拌冰水浴降温至10℃以下，控温10℃以下滴加Boc酸的DCM溶液，滴加结束后在室温下反应2.5 h。TLC检测(展开剂:DCM/MeOH= 20/1，产品的Rf =0.3，I2显色)反应完毕。 3）纯化： 往体系加入50 ml水，加入60 ml二氯甲烷萃取，重复操作两次，合并上述有机相，用饱和食盐水洗涤，无水硫酸钠干燥，过滤，滤液真空浓缩得到粗品. 柱层析纯化(200-300目硅胶)，湿法装柱、湿法上样，以DCM/MeOH=50/1 -DCM/MeOH = 20/1洗脱得到产品，浓缩得类白色固体tert-butyl (4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridine-6-carboxylate。

实验步骤: 投料: 2）反应过程： 将(4aS,7aS)-octahydro-1H-pyrrolo[3,4-b]pyridine、DCM投入500 ml三口瓶中，搅拌冰水浴降温至10℃以下，控温10℃以下滴加Boc酸的DCM溶液，滴加结束后在室温下反应2.5 h。TLC检测(展开剂:DCM/MeOH= 20/1，产品的Rf =0.3，I2显色)反应完毕。 3）纯化： 往体系加入50 ml水，加入60 ml二氯甲烷萃取，重复操作两次，合并上述有机相，用饱和食盐水洗涤，无水硫酸钠干燥，过滤，滤液真空浓缩得到粗品. 柱层析纯化(200-300目硅胶)，湿法装柱、湿法上样，以DCM/MeOH=50/1 -DCM/MeOH = 20/1洗脱得到产品，浓缩得类白色固体tert-butyl (4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridine-6-carboxylate。