1-(benzo[d][1,3]dioxol-5-yl)-N-methylpropan-2-amine [MDMA] by Asch

Query Query

Results

Date

67 reactions in Reaxys

2016-08-22 13h:27m:51s (EST)

H N

1. Query O

Search as: As drawn

1/27

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H N

Rx-ID: 9037704 View in Reaxys 1/67 Yield

Conditions & References

98 %

With lithium aluminium tetrahydride in tetrahydrofuran, Time= 2h, Heating Pizarro, Nieves; De la Torre, Rafael; Farre, Magi; Segura, Jordi; Llebaria, Amadeu; Joglar, Jesus; Bioorganic and Medicinal Chemistry; vol. 10; nb. 4; (2002); p. 1085 - 1092 View in Reaxys 4.1.14. (R)-1-(benzo[d][1,3]dioxol-5-yl)-N-methylpropan-2-amine,(R)-10a, (R)-MDMA General procedure: A solution of (R)-9a (106 mg, 0.42 mmol) in anh THF (5 mL) was added dropwise to a suspension of LiAlH4 (0.048 g, 1.26 mmol,3 equiv) in anh THF (3 mL). The mixture was refluxed with stirring for 4 h and then allowed to cool to room temperature. The excess LiAlH4 was destroyed by slow addition of water at 0 °C. Ethyl acetate was added, extracted with NH4Cl (5 mL) and NaCl (5 mL). The organic layers were dried over anhydrous MgSO4, filtered and the solvent was removed under reduced pressure affording (R)-10a(70 mg, 0.36 mmol) in 85percent of yield as a colourless oil. This compound was then dissolved in anhydrous diethyl ether (4 mL) and 2 M HCl in diethyl ether was added dropwise, yielding the corresponding hydrochloride HCl (R)-10a as a white solid. With lithium aluminium tetrahydride in tetrahydrofuran, Time= 4h, Reflux Llabres, Salome; Garcia-Rates, Sara; Cristobal-Lecina, Edgar; Riera, Antoni; Borrell, Jose Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys O

H N O

O O

Rx-ID: 14955721 View in Reaxys 2/67 Yield

Conditions & References Reaction Steps: 7 1.1: 96 percent / NH4OAc / 17 h / Heating 2.1: 71 percent / LiAlH4 / tetrahydrofuran / 4 h / Heating 3.1: dibenzoyl-L-(-)-tartaric acid / methanol / Heating 3.2: base 4.1: Et3N; DMAP / tetrahydrofuran / 6 h / 20 °C 5.1: 95 percent / H2 / Pd/C / methanol 6.1: 95 percent / cesium carbonate / dimethylformamide / 2 h 7.1: 98 percent / LiAlH4 / tetrahydrofuran / 2 h / Heating With 4-(N,N-dimethlyamino)pyridine, lithium aluminium tetrahydride, ammonium acetate, hydrogen, caesium carbonate, triethylamine, (2R,3S)-(-)-di-O-benzoyl tartaric acid, palladium on activated charcoal in tetrahydrofuran, methanol, N,N-dimethyl-formamide Pizarro, Nieves; De la Torre, Rafael; Farre, Magi; Segura, Jordi; Llebaria, Amadeu; Joglar, Jesus; Bioorganic and Medicinal Chemistry; vol. 10; nb. 4; (2002); p. 1085 - 1092 View in Reaxys Reaction Steps: 9 1: ammonium acetate / 17 h / |Reflux 2: iron; anhydrous iron chloride; hydrogenchloride / water; ethanol / 5 h / |Reflux 3: titanium tetraethoxide / tetrahydrofuran / 5 h / |Reflux 4: sodium tetrahydroborate / tetrahydrofuran / 3 h / -20 - 20 °C 5: hydrogenchloride / methanol; 1,4-dioxane / 20 °C

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6: 4-(N,N-dimethlyamino)pyridine; triethylamine / tetrahydrofuran / 6 h / 0 - 20 °C 7: palladium 10 on activated carbon; hydrogen / methanol / 15 h / 65 °C / 7500.75 Torr 8: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 9: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / |Reflux With hydrogenchloride, 4-(N,N-dimethlyamino)pyridine, anhydrous iron chloride, titanium tetraethoxide, sodium tetrahydroborate, lithium aluminium tetrahydride, palladium 10 on activated carbon, ammonium acetate, hydrogen, iron, caesium carbonate, triethylamine in tetrahydrofuran, 1,4-dioxane, methanol, ethanol, water, N,N-dimethyl-formamide Llabres, Salome; Garcia-Rates, Sara; Cristobal-Lecina, Edgar; Riera, Antoni; Borrell, Jose Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys

H NH 2

H N

Rx-ID: 14971005 View in Reaxys 3/67 Yield

Conditions & References Reaction Steps: 4 1: Et3N; DMAP / tetrahydrofuran / 6 h / 20 °C 2: 95 percent / H2 / Pd/C / methanol 3: 95 percent / cesium carbonate / dimethylformamide / 2 h 4: 98 percent / LiAlH4 / tetrahydrofuran / 2 h / Heating With 4-(N,N-dimethlyamino)pyridine, lithium aluminium tetrahydride, hydrogen, caesium carbonate, triethylamine, palladium on activated charcoal in tetrahydrofuran, methanol, N,N-dimethyl-formamide Pizarro, Nieves; De la Torre, Rafael; Farre, Magi; Segura, Jordi; Llebaria, Amadeu; Joglar, Jesus; Bioorganic and Medicinal Chemistry; vol. 10; nb. 4; (2002); p. 1085 - 1092 View in Reaxys Reaction Steps: 4 1: 4-(N,N-dimethlyamino)pyridine; triethylamine / tetrahydrofuran / 6 h / 0 - 20 °C 2: palladium 10 on activated carbon; hydrogen / methanol / 15 h / 65 °C / 7500.75 Torr 3: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 4: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / |Reflux With 4-(N,N-dimethlyamino)pyridine, lithium aluminium tetrahydride, palladium 10 on activated carbon, hydrogen, caesium carbonate, triethylamine in tetrahydrofuran, methanol, N,N-dimethyl-formamide Llabres, Salome; Garcia-Rates, Sara; Cristobal-Lecina, Edgar; Riera, Antoni; Borrell, Jose Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys

H N

O O

H N

O O

Rx-ID: 14983668 View in Reaxys 4/67 Yield

Conditions & References Reaction Steps: 2 1: 95 percent / cesium carbonate / dimethylformamide / 2 h 2: 98 percent / LiAlH4 / tetrahydrofuran / 2 h / Heating With lithium aluminium tetrahydride, caesium carbonate in tetrahydrofuran, N,N-dimethyl-formamide Pizarro, Nieves; De la Torre, Rafael; Farre, Magi; Segura, Jordi; Llebaria, Amadeu; Joglar, Jesus; Bioorganic and Medicinal Chemistry; vol. 10; nb. 4; (2002); p. 1085 - 1092

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View in Reaxys Reaction Steps: 2 1: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 2: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / |Reflux With lithium aluminium tetrahydride, caesium carbonate in tetrahydrofuran, N,N-dimethyl-formamide Llabres, Salome; Garcia-Rates, Sara; Cristobal-Lecina, Edgar; Riera, Antoni; Borrell, Jose Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys

H N

O O

Rx-ID: 14990048 View in Reaxys 5/67 Yield

Conditions & References Reaction Steps: 3 1: 95 percent / H2 / Pd/C / methanol 2: 95 percent / cesium carbonate / dimethylformamide / 2 h 3: 98 percent / LiAlH4 / tetrahydrofuran / 2 h / Heating With lithium aluminium tetrahydride, hydrogen, caesium carbonate, palladium on activated charcoal in tetrahydrofuran, methanol, N,N-dimethyl-formamide Pizarro, Nieves; De la Torre, Rafael; Farre, Magi; Segura, Jordi; Llebaria, Amadeu; Joglar, Jesus; Bioorganic and Medicinal Chemistry; vol. 10; nb. 4; (2002); p. 1085 - 1092 View in Reaxys Reaction Steps: 3 1: palladium 10 on activated carbon; hydrogen / methanol / 15 h / 65 °C / 7500.75 Torr 2: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 3: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / |Reflux With lithium aluminium tetrahydride, palladium 10 on activated carbon, hydrogen, caesium carbonate in tetrahydrofuran, methanol, N,N-dimethyl-formamide Llabres, Salome; Garcia-Rates, Sara; Cristobal-Lecina, Edgar; Riera, Antoni; Borrell, Jose Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys

H N

O Cl

Rx-ID: 37966350 View in Reaxys 6/67 Yield

Conditions & References Reaction Steps: 4 1: palladium 10 on activated carbon; hydrogen / methanol / 15 h / 65 °C / 7500.75 Torr 2: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C

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3: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / |Reflux 4: hydrogenchloride / diethyl ether With hydrogenchloride, lithium aluminium tetrahydride, palladium 10 on activated carbon, hydrogen, caesium carbonate in tetrahydrofuran, methanol, diethyl ether, N,N-dimethyl-formamide Llabres, Salome; Garcia-Rates, Sara; Cristobal-Lecina, Edgar; Riera, Antoni; Borrell, Jose Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys

H N

O O

Rx-ID: 37966351 View in Reaxys 7/67 Yield

Conditions & References Reaction Steps: 2 1: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 2: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / |Reflux With lithium aluminium tetrahydride, caesium carbonate in tetrahydrofuran, N,N-dimethyl-formamide Llabres, Salome; Garcia-Rates, Sara; Cristobal-Lecina, Edgar; Riera, Antoni; Borrell, Jose Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys

H N

O Cl

Rx-ID: 37966352 View in Reaxys 8/67 Yield

Conditions & References Reaction Steps: 3 1: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 2: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / |Reflux 3: hydrogenchloride / diethyl ether With hydrogenchloride, lithium aluminium tetrahydride, caesium carbonate in tetrahydrofuran, diethyl ether, N,N-dimethyl-formamide Llabres, Salome; Garcia-Rates, Sara; Cristobal-Lecina, Edgar; Riera, Antoni; Borrell, Jose Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys

H N

O O

H N

O Cl

Rx-ID: 37966354 View in Reaxys 9/67 Yield

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Llabres, Salome; Garcia-Rates, Sara; Cristobal-Lecina, Edgar; Riera, Antoni; Borrell, Jose Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys

H N

O O

Rx-ID: 37966355 View in Reaxys 10/67 Yield

Conditions & References

85 %

4.1.14. (R)-1-(benzo[d][1,3]dioxol-5-yl)-N-methylpropan-2-amine,(R)-10a, (R)-MDMA A solution of (R)-9a (106 mg, 0.42 mmol) in anh THF (5 mL) was added dropwise to a suspension of LiAlH4 (0.048 g, 1.26 mmol,3 equiv) in anh THF (3 mL). The mixture was refluxed with stirring for 4 h and then allowed to cool to room temperature. The excess LiAlH4 was destroyed by slow addition of water at 0 °C. Ethyl acetate was added, extracted with NH4Cl (5 mL) and NaCl (5 mL). The organic layers were dried over anhydrous MgSO4, filtered and the solvent was removed under reduced pressure affording (R)-10a(70 mg, 0.36 mmol) in 85percent of yield as a colourless oil. This compound was then dissolved in anhydrous diethyl ether (4 mL) and 2 M HCl in diethyl ether was added dropwise, yielding the corresponding hydrochloride HCl (R)-10a as a white solid. With lithium aluminium tetrahydride in tetrahydrofuran, Time= 4h, Reflux Llabres, Salome; Garcia-Rates, Sara; Cristobal-Lecina, Edgar; Riera, Antoni; Borrell, Jose Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys

H N

O Cl

Rx-ID: 37966356 View in Reaxys 11/67 Yield

Conditions & References Reaction Steps: 2 1: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / |Reflux 2: hydrogenchloride / diethyl ether With hydrogenchloride, lithium aluminium tetrahydride in tetrahydrofuran, diethyl ether Llabres, Salome; Garcia-Rates, Sara; Cristobal-Lecina, Edgar; Riera, Antoni; Borrell, Jose Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys

H N

O O

H N

O Cl

Rx-ID: 37966357 View in Reaxys 12/67 Yield

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H N

O Cl

Rx-ID: 37966358 View in Reaxys 13/67 Yield

Conditions & References 4.1.14. (R)-1-(benzo[d][1,3]dioxol-5-yl)-N-methylpropan-2-amine,(R)-10a, (R)-MDMA A solution of (R)-9a (106 mg, 0.42 mmol) in anh THF (5 mL) was added dropwise to a suspension of LiAlH4 (0.048 g, 1.26 mmol,3 equiv) in anh THF (3 mL). The mixture was refluxed with stirring for 4 h and then allowed to cool to room temperature. The excess LiAlH4 was destroyed by slow addition of water at 0 °C. Ethyl acetate was added, extracted with NH4Cl (5 mL) and NaCl (5 mL). The organic layers were dried over anhydrous MgSO4, filtered and the solvent was removed under reduced pressure affording (R)-10a(70 mg, 0.36 mmol) in 85percent of yield as a colourless oil. This compound was then dissolved in anhydrous diethyl ether (4 mL) and 2 M HCl in diethyl ether was added dropwise, yielding the corresponding hydrochloride HCl (R)-10a as a white solid. With hydrogenchloride in diethyl ether Llabres, Salome; Garcia-Rates, Sara; Cristobal-Lecina, Edgar; Riera, Antoni; Borrell, Jose Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys

H N

O Cl

Rx-ID: 37966359 View in Reaxys 14/67 Yield

Conditions & References

41 mg

4.1.14. (R)-1-(benzo[d][1,3]dioxol-5-yl)-N-methylpropan-2-amine,(R)-10a, (R)-MDMA General procedure: A solution of (R)-9a (106 mg, 0.42 mmol) in anh THF (5 mL) was added dropwise to a suspension of LiAlH4 (0.048 g, 1.26 mmol,3 equiv) in anh THF (3 mL). The mixture was refluxed with stirring for 4 h and then allowed to cool to room temperature. The excess LiAlH4 was destroyed by slow addition of water at 0 °C. Ethyl acetate was added, extracted with NH4Cl (5 mL) and NaCl (5 mL). The organic layers were dried over anhydrous MgSO4, filtered and the solvent was removed under reduced pressure affording (R)-10a(70 mg, 0.36 mmol) in 85percent of yield as a colourless oil. This compound was then dissolved in anhydrous diethyl ether (4 mL) and 2 M HCl in diethyl ether was added dropwise, yielding the corresponding hydrochloride HCl (R)-10a as a white solid. With hydrogenchloride in diethyl ether Llabres, Salome; Garcia-Rates, Sara; Cristobal-Lecina, Edgar; Riera, Antoni; Borrell, Jose Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys O

H N O

O O

Rx-ID: 37966362 View in Reaxys 15/67 Yield

Conditions & References Reaction Steps: 9 1: ammonium acetate / 17 h / |Reflux 2: iron; anhydrous iron chloride; hydrogenchloride / water; ethanol / 5 h / |Reflux 3: titanium tetraethoxide / tetrahydrofuran / 5 h / |Reflux 4: sodium tetrahydroborate / tetrahydrofuran / 3 h / -20 - 20 °C 5: hydrogenchloride / methanol; 1,4-dioxane / 20 °C

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H N O

O Cl

Rx-ID: 37966366 View in Reaxys 16/67 Yield

Conditions & References Reaction Steps: 10 1: ammonium acetate / 17 h / |Reflux 2: iron; anhydrous iron chloride; hydrogenchloride / water; ethanol / 5 h / |Reflux 3: titanium tetraethoxide / tetrahydrofuran / 5 h / |Reflux 4: sodium tetrahydroborate / tetrahydrofuran / 3 h / -20 - 20 °C 5: hydrogenchloride / methanol; 1,4-dioxane / 20 °C 6: 4-(N,N-dimethlyamino)pyridine; triethylamine / tetrahydrofuran / 6 h / 0 - 20 °C 7: palladium 10 on activated carbon; hydrogen / methanol / 15 h / 65 °C / 7500.75 Torr 8: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 9: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / |Reflux 10: hydrogenchloride / diethyl ether With hydrogenchloride, 4-(N,N-dimethlyamino)pyridine, anhydrous iron chloride, titanium tetraethoxide, sodium tetrahydroborate, lithium aluminium tetrahydride, palladium 10 on activated carbon, ammonium acetate, hydrogen, iron, caesium carbonate, triethylamine in tetrahydrofuran, 1,4-dioxane, methanol, diethyl ether, ethanol, water, N,N-dimethyl-formamide Llabres, Salome; Garcia-Rates, Sara; Cristobal-Lecina, Edgar; Riera, Antoni; Borrell, Jose Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys O

H N O

O Cl

Rx-ID: 37966367 View in Reaxys 17/67 Yield

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8: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 9: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / |Reflux 10: hydrogenchloride / diethyl ether With hydrogenchloride, 4-(N,N-dimethlyamino)pyridine, anhydrous iron chloride, titanium tetraethoxide, sodium tetrahydroborate, lithium aluminium tetrahydride, palladium 10 on activated carbon, ammonium acetate, hydrogen, iron, caesium carbonate, triethylamine in tetrahydrofuran, 1,4-dioxane, methanol, diethyl ether, ethanol, water, N,N-dimethyl-formamide Llabres, Salome; Garcia-Rates, Sara; Cristobal-Lecina, Edgar; Riera, Antoni; Borrell, Jose Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys O E

N O

H N

O O

Rx-ID: 37966376 View in Reaxys 18/67 Yield

Conditions & References Reaction Steps: 8 1: iron; anhydrous iron chloride; hydrogenchloride / water; ethanol / 5 h / |Reflux 2: titanium tetraethoxide / tetrahydrofuran / 5 h / |Reflux 3: sodium tetrahydroborate / tetrahydrofuran / 3 h / -20 - 20 °C 4: hydrogenchloride / methanol; 1,4-dioxane / 20 °C 5: 4-(N,N-dimethlyamino)pyridine; triethylamine / tetrahydrofuran / 6 h / 0 - 20 °C 6: palladium 10 on activated carbon; hydrogen / methanol / 15 h / 65 °C / 7500.75 Torr 7: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 8: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / |Reflux With hydrogenchloride, 4-(N,N-dimethlyamino)pyridine, anhydrous iron chloride, titanium tetraethoxide, sodium tetrahydroborate, lithium aluminium tetrahydride, palladium 10 on activated carbon, hydrogen, iron, caesium carbonate, triethylamine in tetrahydrofuran, 1,4-dioxane, methanol, ethanol, water, N,N-dimethyl-formamide Llabres, Salome; Garcia-Rates, Sara; Cristobal-Lecina, Edgar; Riera, Antoni; Borrell, Jose Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys O E

N O

H N

O O

Rx-ID: 37966377 View in Reaxys 19/67 Yield

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With hydrogenchloride, 4-(N,N-dimethlyamino)pyridine, anhydrous iron chloride, titanium tetraethoxide, sodium tetrahydroborate, lithium aluminium tetrahydride, palladium 10 on activated carbon, hydrogen, iron, caesium carbonate, triethylamine in tetrahydrofuran, 1,4-dioxane, methanol, ethanol, water, N,N-dimethyl-formamide Llabres, Salome; Garcia-Rates, Sara; Cristobal-Lecina, Edgar; Riera, Antoni; Borrell, Jose Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys O E

N O

H N

O Cl

Rx-ID: 37966382 View in Reaxys 20/67 Yield

Conditions & References Reaction Steps: 9 1: iron; anhydrous iron chloride; hydrogenchloride / water; ethanol / 5 h / |Reflux 2: titanium tetraethoxide / tetrahydrofuran / 5 h / |Reflux 3: sodium tetrahydroborate / tetrahydrofuran / 3 h / -20 - 20 °C 4: hydrogenchloride / methanol; 1,4-dioxane / 20 °C 5: 4-(N,N-dimethlyamino)pyridine; triethylamine / tetrahydrofuran / 6 h / 0 - 20 °C 6: palladium 10 on activated carbon; hydrogen / methanol / 15 h / 65 °C / 7500.75 Torr 7: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 8: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / |Reflux 9: hydrogenchloride / diethyl ether With hydrogenchloride, 4-(N,N-dimethlyamino)pyridine, anhydrous iron chloride, titanium tetraethoxide, sodium tetrahydroborate, lithium aluminium tetrahydride, palladium 10 on activated carbon, hydrogen, iron, caesium carbonate, triethylamine in tetrahydrofuran, 1,4-dioxane, methanol, diethyl ether, ethanol, water, N,N-dimethyl-formamide Llabres, Salome; Garcia-Rates, Sara; Cristobal-Lecina, Edgar; Riera, Antoni; Borrell, Jose Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys O E

N O

H N

O Cl

Rx-ID: 37966383 View in Reaxys 21/67 Yield

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H N O

Rx-ID: 37966391 View in Reaxys 22/67 Yield

Conditions & References Reaction Steps: 6 1: sodium tetrahydroborate / tetrahydrofuran / 3 h / -20 - 20 °C 2: hydrogenchloride / methanol; 1,4-dioxane / 20 °C 3: 4-(N,N-dimethlyamino)pyridine; triethylamine / tetrahydrofuran / 6 h / 0 - 20 °C 4: palladium 10 on activated carbon; hydrogen / methanol / 15 h / 65 °C / 7500.75 Torr 5: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 6: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / |Reflux With hydrogenchloride, 4-(N,N-dimethlyamino)pyridine, sodium tetrahydroborate, lithium aluminium tetrahydride, palladium 10 on activated carbon, hydrogen, caesium carbonate, triethylamine in tetrahydrofuran, 1,4-dioxane, methanol, N,N-dimethyl-formamide Llabres, Salome; Garcia-Rates, Sara; Cristobal-Lecina, Edgar; Riera, Antoni; Borrell, Jose Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys

H N O

O Cl

S O

Rx-ID: 37966393 View in Reaxys 23/67 Yield

Conditions & References Reaction Steps: 7 1: sodium tetrahydroborate / tetrahydrofuran / 3 h / -20 - 20 °C 2: hydrogenchloride / methanol; 1,4-dioxane / 20 °C 3: 4-(N,N-dimethlyamino)pyridine; triethylamine / tetrahydrofuran / 6 h / 0 - 20 °C 4: palladium 10 on activated carbon; hydrogen / methanol / 15 h / 65 °C / 7500.75 Torr 5: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 6: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / |Reflux 7: hydrogenchloride / diethyl ether With hydrogenchloride, 4-(N,N-dimethlyamino)pyridine, sodium tetrahydroborate, lithium aluminium tetrahydride, palladium 10 on activated carbon, hydrogen, caesium carbonate, triethylamine in tetrahydrofuran, 1,4-dioxane, methanol, diethyl ether, N,N-dimethyl-formamide Llabres, Salome; Garcia-Rates, Sara; Cristobal-Lecina, Edgar; Riera, Antoni; Borrell, Jose Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys

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H N O

Rx-ID: 37966400 View in Reaxys 24/67 Yield

H N O

O Cl

S O

Rx-ID: 37966401 View in Reaxys 25/67 Yield

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O O

H N O

O O

Rx-ID: 37966409 View in Reaxys 26/67 Yield

Conditions & References Reaction Steps: 7 1: titanium tetraethoxide / tetrahydrofuran / 5 h / |Reflux 2: sodium tetrahydroborate / tetrahydrofuran / 3 h / -20 - 20 °C 3: hydrogenchloride / methanol; 1,4-dioxane / 20 °C 4: 4-(N,N-dimethlyamino)pyridine; triethylamine / tetrahydrofuran / 6 h / 0 - 20 °C 5: palladium 10 on activated carbon; hydrogen / methanol / 15 h / 65 °C / 7500.75 Torr 6: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 7: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / |Reflux With hydrogenchloride, 4-(N,N-dimethlyamino)pyridine, titanium tetraethoxide, sodium tetrahydroborate, lithium aluminium tetrahydride, palladium 10 on activated carbon, hydrogen, caesium carbonate, triethylamine in tetrahydrofuran, 1,4-dioxane, methanol, N,N-dimethyl-formamide Llabres, Salome; Garcia-Rates, Sara; Cristobal-Lecina, Edgar; Riera, Antoni; Borrell, Jose Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys

O O

H N O

O O

Rx-ID: 37966410 View in Reaxys 27/67 Yield

O O

H N O

O Cl

Rx-ID: 37966412 View in Reaxys 28/67

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Yield

Conditions & References Reaction Steps: 8 1: titanium tetraethoxide / tetrahydrofuran / 5 h / |Reflux 2: sodium tetrahydroborate / tetrahydrofuran / 3 h / -20 - 20 °C 3: hydrogenchloride / methanol; 1,4-dioxane / 20 °C 4: 4-(N,N-dimethlyamino)pyridine; triethylamine / tetrahydrofuran / 6 h / 0 - 20 °C 5: palladium 10 on activated carbon; hydrogen / methanol / 15 h / 65 °C / 7500.75 Torr 6: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 7: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / |Reflux 8: hydrogenchloride / diethyl ether With hydrogenchloride, 4-(N,N-dimethlyamino)pyridine, titanium tetraethoxide, sodium tetrahydroborate, lithium aluminium tetrahydride, palladium 10 on activated carbon, hydrogen, caesium carbonate, triethylamine in tetrahydrofuran, 1,4-dioxane, methanol, diethyl ether, N,N-dimethyl-formamide Llabres, Salome; Garcia-Rates, Sara; Cristobal-Lecina, Edgar; Riera, Antoni; Borrell, Jose Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys

O O

H N

Rx-ID: 37966413 View in Reaxys 29/67 Yield

H N

S O

Rx-ID: 37966424 View in Reaxys 30/67 Yield

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4: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 5: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / |Reflux With hydrogenchloride, 4-(N,N-dimethlyamino)pyridine, lithium aluminium tetrahydride, palladium 10 on activated carbon, hydrogen, caesium carbonate, triethylamine in tetrahydrofuran, 1,4-dioxane, methanol, N,N-dimethyl-formamide Llabres, Salome; Garcia-Rates, Sara; Cristobal-Lecina, Edgar; Riera, Antoni; Borrell, Jose Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys

H N

Rx-ID: 37966425 View in Reaxys 31/67 Yield

Conditions & References Reaction Steps: 6 1: hydrogenchloride / methanol; 1,4-dioxane / 20 °C 2: 4-(N,N-dimethlyamino)pyridine; triethylamine / tetrahydrofuran / 6 h / 0 - 20 °C 3: palladium 10 on activated carbon; hydrogen / methanol / 15 h / 65 °C / 7500.75 Torr 4: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 5: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / |Reflux 6: hydrogenchloride / diethyl ether With hydrogenchloride, 4-(N,N-dimethlyamino)pyridine, lithium aluminium tetrahydride, palladium 10 on activated carbon, hydrogen, caesium carbonate, triethylamine in tetrahydrofuran, 1,4-dioxane, methanol, diethyl ether, N,N-dimethyl-formamide Llabres, Salome; Garcia-Rates, Sara; Cristobal-Lecina, Edgar; Riera, Antoni; Borrell, Jose Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys

H N

S O

Rx-ID: 37966431 View in Reaxys 32/67 Yield

Conditions & References Reaction Steps: 5 1: hydrogenchloride / methanol; 1,4-dioxane / 20 °C 2: 4-(N,N-dimethlyamino)pyridine; triethylamine / tetrahydrofuran / 6 h / 0 - 20 °C 3: palladium 10 on activated carbon; hydrogen / methanol / 15 h / 65 °C / 7500.75 Torr 4: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 5: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / |Reflux With hydrogenchloride, 4-(N,N-dimethlyamino)pyridine, lithium aluminium tetrahydride, palladium 10 on activated carbon, hydrogen, caesium carbonate, triethylamine in tetrahydrofuran, 1,4-dioxane, methanol, N,N-dimethyl-formamide Llabres, Salome; Garcia-Rates, Sara; Cristobal-Lecina, Edgar; Riera, Antoni; Borrell, Jose Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46

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View in Reaxys

H N

O Cl

Rx-ID: 37966432 View in Reaxys 33/67 Yield

H NH 2

H N

Rx-ID: 37966436 View in Reaxys 34/67 Yield

Conditions & References Reaction Steps: 4 1: 4-(N,N-dimethlyamino)pyridine; triethylamine / tetrahydrofuran / 6 h / 0 - 20 °C 2: palladium 10 on activated carbon; hydrogen / methanol / 15 h / 65 °C / 7500.75 Torr 3: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 4: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / |Reflux With 4-(N,N-dimethlyamino)pyridine, lithium aluminium tetrahydride, palladium 10 on activated carbon, hydrogen, caesium carbonate, triethylamine in tetrahydrofuran, methanol, N,N-dimethyl-formamide Llabres, Salome; Garcia-Rates, Sara; Cristobal-Lecina, Edgar; Riera, Antoni; Borrell, Jose Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys

H NH 2

H N

O Cl

Rx-ID: 37966437 View in Reaxys 35/67

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Yield

Conditions & References Reaction Steps: 5 1: 4-(N,N-dimethlyamino)pyridine; triethylamine / tetrahydrofuran / 6 h / 0 - 20 °C 2: palladium 10 on activated carbon; hydrogen / methanol / 15 h / 65 °C / 7500.75 Torr 3: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 4: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / |Reflux 5: hydrogenchloride / diethyl ether With hydrogenchloride, 4-(N,N-dimethlyamino)pyridine, lithium aluminium tetrahydride, palladium 10 on activated carbon, hydrogen, caesium carbonate, triethylamine in tetrahydrofuran, methanol, diethyl ether, N,N-dimethyl-formamide Llabres, Salome; Garcia-Rates, Sara; Cristobal-Lecina, Edgar; Riera, Antoni; Borrell, Jose Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys

H NH 2

H N

O Cl

Rx-ID: 37966438 View in Reaxys 36/67 Yield

H N

Rx-ID: 37966441 View in Reaxys 37/67 Yield

Conditions & References Reaction Steps: 3 1: palladium 10 on activated carbon; hydrogen / methanol / 15 h / 65 °C / 7500.75 Torr 2: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 3: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / |Reflux With lithium aluminium tetrahydride, palladium 10 on activated carbon, hydrogen, caesium carbonate in tetrahydrofuran, methanol, N,N-dimethyl-formamide

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H N

Rx-ID: 37966442 View in Reaxys 38/67 Yield

Conditions & References Reaction Steps: 4 1: palladium 10 on activated carbon; hydrogen / methanol / 15 h / 65 °C / 7500.75 Torr 2: caesium carbonate / N,N-dimethyl-formamide / 2 h / 20 °C 3: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / |Reflux 4: hydrogenchloride / diethyl ether With hydrogenchloride, lithium aluminium tetrahydride, palladium 10 on activated carbon, hydrogen, caesium carbonate in tetrahydrofuran, methanol, diethyl ether, N,N-dimethyl-formamide Llabres, Salome; Garcia-Rates, Sara; Cristobal-Lecina, Edgar; Riera, Antoni; Borrell, Jose Ignacio; Camarasa, Jorge; Pubill, David; Luque, F. Javier; Escubedo, Elena; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 35 - 46 View in Reaxys H

O 13 C O

13C

O 13 C

13C 13CH

NH 2

13C

13C 13CH

HCl

Rx-ID: 38014751 View in Reaxys 39/67 Yield 86 %

Conditions & References Stage 1:Time= 2h, T= 100 °C , Autoclave Stage 2: With lithium aluminium tetrahydride in diethyl ether, Time= 5h, Reflux Stage 3: With hydrogenchloride in diethyl ether, isopropyl alcohol, T= 10 °C , pH= 4 Karlsen, Morten; Liu, Huiling; Berg, Thomas; Johansen, Jon Eigill; Hoff, Bard Helge; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 57; nb. 5; (2014); p. 378 - 387 View in Reaxys

H 13C 13CH 13CH HO 13C H 13C 13CH

O 13 C O

13C

13C 13CH

HCl

Rx-ID: 38014774 View in Reaxys 40/67 Yield

Conditions & References Reaction Steps: 6 1.1: magnesium methanolate / toluene / 40 - 75 °C / |Inert atmosphere 1.2: 95 - 100 °C 2.1: sodium hydroxide; dihydrogen peroxide / water / 30 - 40 °C / |Inert atmosphere 3.1: caesium carbonate / dimethyl sulfoxide / 2 h / 80 °C / |Inert atmosphere 4.1: N-bromosuccinmide / chloroform / 2 h / |Reflux 5.1: tris-(o-tolyl)phosphine; tri-n-butyltin methoxide; palladium dichloride / toluene / 4 h / 90 °C / |Inert atmosphere 6.1: ethanol; methanol / 2 h / |Molecular sieve 6.3: 10 °C / pH 4 With N-bromosuccinmide, dihydrogen peroxide, tri-n-butyltin methoxide, caesium carbonate, magnesium methanolate, tris-(o-tolyl)phosphine, sodium hydroxide, palladium dichloride in methanol, ethanol, chloroform, water, dimethyl sulfoxide, toluene, 2.1: |Dakin Phenol Oxidation

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Karlsen, Morten; Liu, Huiling; Berg, Thomas; Johansen, Jon Eigill; Hoff, Bard Helge; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 57; nb. 5; (2014); p. 378 - 387 View in Reaxys H

H 13C H 13C

13C

O 13 C

13C

13C 13CH

HCl

Rx-ID: 38014804 View in Reaxys 41/67 Yield

Conditions & References Reaction Steps: 5 1.1: sodium hydroxide; dihydrogen peroxide / water / 30 - 40 °C / |Inert atmosphere 2.1: caesium carbonate / dimethyl sulfoxide / 2 h / 80 °C / |Inert atmosphere 3.1: N-bromosuccinmide / chloroform / 2 h / |Reflux 4.1: tris-(o-tolyl)phosphine; tri-n-butyltin methoxide; palladium dichloride / toluene / 4 h / 90 °C / |Inert atmosphere 5.1: ethanol; methanol / 2 h / |Molecular sieve 5.3: 10 °C / pH 4 With N-bromosuccinmide, dihydrogen peroxide, tri-n-butyltin methoxide, caesium carbonate, tris-(o-tolyl)phosphine, sodium hydroxide, palladium dichloride in methanol, ethanol, chloroform, water, dimethyl sulfoxide, toluene, 1.1: |Dakin Phenol Oxidation Karlsen, Morten; Liu, Huiling; Berg, Thomas; Johansen, Jon Eigill; Hoff, Bard Helge; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 57; nb. 5; (2014); p. 378 - 387 View in Reaxys

13C 13C

13C

O 13 C

13CH 13CH

13C

13C 13CH

HCl

Rx-ID: 38014809 View in Reaxys 42/67 Yield

Conditions & References Reaction Steps: 4 1.1: caesium carbonate / dimethyl sulfoxide / 2 h / 80 °C / |Inert atmosphere 2.1: N-bromosuccinmide / chloroform / 2 h / |Reflux 3.1: tris-(o-tolyl)phosphine; tri-n-butyltin methoxide; palladium dichloride / toluene / 4 h / 90 °C / |Inert atmosphere 4.1: ethanol; methanol / 2 h / |Molecular sieve 4.3: 10 °C / pH 4 With N-bromosuccinmide, tri-n-butyltin methoxide, caesium carbonate, tris-(o-tolyl)phosphine, palladium dichloride in methanol, ethanol, chloroform, dimethyl sulfoxide, toluene Karlsen, Morten; Liu, Huiling; Berg, Thomas; Johansen, Jon Eigill; Hoff, Bard Helge; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 57; nb. 5; (2014); p. 378 - 387 View in Reaxys

O 13 C O

13C

H C

13C

13CH

O 13 C O

13C

13C 13CH

HCl

Rx-ID: 38014818 View in Reaxys 43/67 Yield

Conditions & References Reaction Steps: 3 1.1: N-bromosuccinmide / chloroform / 2 h / |Reflux 2.1: tris-(o-tolyl)phosphine; tri-n-butyltin methoxide; palladium dichloride / toluene / 4 h / 90 °C / |Inert atmosphere 3.1: ethanol; methanol / 2 h / |Molecular sieve 3.3: 10 °C / pH 4 With N-bromosuccinmide, tri-n-butyltin methoxide, tris-(o-tolyl)phosphine, palladium dichloride in methanol, ethanol, chloroform, toluene Karlsen, Morten; Liu, Huiling; Berg, Thomas; Johansen, Jon Eigill; Hoff, Bard Helge; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 57; nb. 5; (2014); p. 378 - 387

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View in Reaxys H

H 13C Br O 13 13C C O

13C

O 13 C

13CH

13C

13CH

HCl

Rx-ID: 38014821 View in Reaxys 44/67 Yield

Conditions & References Reaction Steps: 2 1.1: tris-(o-tolyl)phosphine; tri-n-butyltin methoxide; palladium dichloride / toluene / 4 h / 90 °C / |Inert atmosphere 2.1: ethanol; methanol / 2 h / |Molecular sieve 2.3: 10 °C / pH 4 With tri-n-butyltin methoxide, tris-(o-tolyl)phosphine, palladium dichloride in methanol, ethanol, toluene Karlsen, Morten; Liu, Huiling; Berg, Thomas; Johansen, Jon Eigill; Hoff, Bard Helge; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 57; nb. 5; (2014); p. 378 - 387 View in Reaxys H

O 13 C O

13C

O 13 C

H 2N

13CH

13C

13C 13CH

HCl

Rx-ID: 38014825 View in Reaxys 45/67 Yield

Conditions & References

540 mg

Stage 1: in methanol, ethanol, Time= 2h, Molecular sieve Stage 2: With methanol, sodium tetrahydroborate in ethanol Stage 3: With hydrogenchloride in diethyl ether, isopropyl alcohol, T= 10 °C , pH= 4 Karlsen, Morten; Liu, Huiling; Berg, Thomas; Johansen, Jon Eigill; Hoff, Bard Helge; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 57; nb. 5; (2014); p. 378 - 387 View in Reaxys

H N

O O

Rx-ID: 38364357 View in Reaxys 46/67 Yield

Conditions & References With column LiChrospher 100 RP-18e, sulfated β-cyclodextrin in methanol, water, T= 20 °C , Reagent/catalyst Taschwer, Magdalena; Seidl, Yvonne; Mohr, Stefan; Schmid, Martin G.; Chirality; vol. 26; nb. 8; (2014); p. 411 418 View in Reaxys

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H N O H N

H N

O O

O H N

H N

Rx-ID: 32780624 View in Reaxys 47/67 Yield

Conditions & References in water, dimethyl sulfoxide, T= 25 °C , Kinetics Moreno, Daniel; Grenu, Borja Diaz De; Garcia, Begona; Ibeas, Saturnino; Torroba, Tomas; Chemical Communications; vol. 48; nb. 24; (2012); p. 2994 - 2996 View in Reaxys

H N

Rx-ID: 29474950 View in Reaxys 48/67 Yield

Conditions & References Stage 1: With hydrogenchloride in tetrahydrofuran, water, Time= 3h, T= 45 °C Stage 2: With potassium carbonate in water Schulze, Matthias; Synthetic Communications; vol. 40; nb. 10; (2010); p. 1461 - 1476 View in Reaxys H N

HO OH

H N

OH O

Rx-ID: 29474958 View in Reaxys 49/67

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Yield

Conditions & References

76 %

in ethanol, Time= 0.5h Schulze, Matthias; Synthetic Communications; vol. 40; nb. 10; (2010); p. 1461 - 1476 View in Reaxys H N

H 2N O

Rx-ID: 1835346 View in Reaxys 50/67 Yield

Conditions & References

78 %

Stage 1: in ethanol, water, Time= 1h, T= 20 °C Stage 2: With hydrogen, platinum(IV) oxide in ethanol, water, Time= 3.5h, p= 2896.11Torr , Further stages. Buchanan, Hilary A. S.; Daeid, Niamh Nic; Meier-Augenstein, Wolfram; Kemp, Helen F.; Kerr, William J.; Middleditch, Michael; Analytical Chemistry; vol. 80; nb. 9; (2008); p. 3350 - 3356 View in Reaxys

74 %

With sodium cyanoborohydride Braun; Shulgin; Arzneimittel-Forschung; vol. 30; nb. 5; (1980); p. 825 - 830 View in Reaxys With sodium cyanoborohydride in methanol Pifl, Christian; Nagy, Gabor; Berenyi, Sandor; Kattinger, Alexandra; Reither, Harald; Antus, Sandor; Journal of Pharmacology and Experimental Therapeutics; vol. 314; nb. 1; (2005); p. 346 - 354 View in Reaxys

2H 2H

H N

2H 2H

H N HCl

Rx-ID: 10841269 View in Reaxys 51/67 Yield

Conditions & References

76 %

2; 10 :00233] A suspension of lithium aluminum hydride (3.5 g, 91.3 mmol) in anhydrous tetrahydrofuran (100 mL) was added dropwise to a solution of d2-N-ethoxycarbonyl-l-(3,4- methylenedioxyphenyl)-2-aminopropane (7.7 g, 30.4 mmol) in anhydrous tetrahydrofuran (80 mL). The mixture was heated to reflux for 2 hours, cooled to ambient temperature, and quenched with water. The organic layer was separated, dried over anhydrous sodium sulfate, filtered, and the solvent was removed to yield the title compound (4.4 g, 76percent yield), which was dissolved in anhydrous diethyl ether and treated with hydrochloric gas to afford d2-3,4- methylenedioxyphenyl-2-aminopropane hydrochloride salt (5 g), as a white solid. 1H NMR (300MHz, CDCl3), δ 9.67 (s, 2H), 6.76-6.66 (m, 3H), 3.40-3.27 (m, 3H), 2.81-2.77 (m, IH), 2.70 (s, 3H), 1.35 (d, 3H, 7=6.6 Hz); LC-MS: m/z=196 [M+H]+. Stage 1: With lithium aluminium tetrahydride in tetrahydrofuran, Time= 2h, Heating / reflux Stage 2: With water in tetrahydrofuran Stage 3: With hydrogenchloride in diethyl ether Patent; AUSPEX PHARMACEUTICALS, INC.; WO2008/16677; (2008); (A2) English View in Reaxys

2H 2H

H N

2H 2H

HCl

Rx-ID: 10841270 View in Reaxys 52/67 Yield

Conditions & References 11 Patent; AUSPEX PHARMACEUTICALS, INC.; WO2008/16677; (2008); (A2) English

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View in Reaxys

2H 2H

H N

2H 2H

H N

2H 2H

Rx-ID: 10841271 View in Reaxys 53/67 Yield

Conditions & References 15; 16 :[00238] The procedure is carried out using the methods described by PojerTetrahedron Letters 1984, 25(23), 2507-2508 and references cited therein. A stirred solution of d5-N-methyl-l-[3,4-methylenedioxyphenyl]-2-aminopropane (0.1 g) is heated at 70-1000C for 18 hours with deuterated Raney nickel (2 mL wet) in tetrahydrofuran or deuterium oxide (5 mL). The reaction is cooled, filtered to remove the Raney nickel and the residue is treated with dilute deuterium chloride in deuterium oxide and extracted into ethyl acetate. The organic layer is dried over sodium sulfate, filtered and the solvent is removed under reduced pressure to give the title product; Example 16 Deuterated Raney Nickel[00239] The procedure is carried out using the methods described by Khan, J. Am.Chem. Soc. 1952, 74, 3018-3022 and references cited therein. Raney nickel (25 g, still wet with dioxane) is washed once with a 25 mL portion of dioxane by centrifugation and the nickel is then suspended in 10 mL of deuterium oxide and allowed to stand in a stoppered tube for 48 hours. The nickel is occasionally stirred a few times throughout the equilibration period. It is then washed with three 25 mL portions of dioxane and transferred to the reaction vessel of a Joshel apparatus (250 mL) with the help of about 125 mL of dioxane. To this catalyst in the reaction vessel is added 5 mL of deuterium oxide. The stopcock above the reaction vessel is then closed, the system evacuated and deuterium gas introduced. About 100 mL of deuterium gas is collected in the 500 mL reservoir. After closing all stopcocks to the outside, the stopcock over the reaction vessel is opened and the catalyst in dioxane is agitated in the presence of deuterium gas under slight pressure for two hours. The process is repeated three times, the system being flushed each time with dry oxygen-free nitrogen and filled with fresh deuterium. Nickel prepared in this manner is stored in purified dioxane containing a small amount of deuterium oxide. Stage 1: With deuterated Raney nickel, Time= 18h, T= 70 - 100 °C Stage 2: With DCl in water-d2 Patent; AUSPEX PHARMACEUTICALS, INC.; WO2008/16677; (2008); (A2) English View in Reaxys H N

rhodaninoic acid

O O

Rx-ID: 13040271 View in Reaxys 54/67 Yield

Conditions & References Reaction Steps: 3 1: NH4OAc / Heating 2: Iron; FeCl3; HCl / Heating 3: NaBH3CN / methanol With hydrogenchloride, ammonium acetate, iron(III) chloride, iron, sodium cyanoborohydride in methanol Pifl, Christian; Nagy, Gabor; Berenyi, Sandor; Kattinger, Alexandra; Reither, Harald; Antus, Sandor; Journal of Pharmacology and Experimental Therapeutics; vol. 314; nb. 1; (2005); p. 346 - 354 View in Reaxys

O O

H N

O O

Rx-ID: 13043127 View in Reaxys 55/67 Yield

Conditions & References Reaction Steps: 2 1: Iron; FeCl3; HCl / Heating 2: NaBH3CN / methanol With hydrogenchloride, iron(III) chloride, iron, sodium cyanoborohydride in methanol

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Pifl, Christian; Nagy, Gabor; Berenyi, Sandor; Kattinger, Alexandra; Reither, Harald; Antus, Sandor; Journal of Pharmacology and Experimental Therapeutics; vol. 314; nb. 1; (2005); p. 346 - 354 View in Reaxys H N

O O

Rx-ID: 5452498 View in Reaxys 56/67 Yield

Conditions & References α-(3,4-Methylendioxyphenyl)-β-brompropan, ethanol. MeNH2-Loesg., Erhitzen im zugeschmolzenen Rohr Biniecki; Krajewski; Acta Poloniae Pharmaceutica; vol. 17; (1960); p. 421,422, 423; ; vol. 55; nb. 14350; (1961) View in Reaxys α-(3,4-Methylendioxyphenyl)-β-brompropan, Methylamin/A. (Erhitzen im zugeschmolzenen Rohr) Biniecki; Krajewski; Acta Poloniae Pharmaceutica; vol. 17; (1960); p. 421,422, 423; ; vol. 55; nb. 14350; (1961) View in Reaxys 2 : Preparation of 3,4-methylenedioxymethamphetamine (MDMA) 1 Example-2 Preparation of 3,4-methylenedioxymethamphetamine (MDMA) 1 Compound 5 (4 g, 0.022 mol) was dissolved in methanol (100 ml) and to this stirred solution was added, methylamine hydrochloride (15.16 g, 0.22 mol) and triethylamine (6.76 ml, 0.049 mol). Sodium cyanoborohydride (1.41 g, 0.022 mol) in methanol (10 ml) was added in one portion and the reaction mixture stirred at room temperature overnight. The solvents were removed in vacuo, water (50 ml) followed by 1N HCl (50 ml) was added and the mixture washed with diethyl ether (100 ml). The aqueous phase was basified to pH 12-13 with 2N NaOH and extracted with ethyl acetate (3*100 ml). The combined organic extracts were dried over sodium sulphate, filtered and the solvent was removed to give crude MDMA (compound 1) free base as brown oil in good yield. The crude product obtained was used without further purification. FT-IR (film, neat): 3172, 2779.3, 2715.4, 1246.7 and 1037.9 cm-1 () Patent; McConnell, Robert Ivan; Benchikh, Elouard; Fitzgerald, Stephen Peter; Lamont, John Victor; US2004/121400; (2004); (A1) English View in Reaxys

NH 2 O

H N O

O O

Rx-ID: 14960803 View in Reaxys 57/67 Yield

Conditions & References Reaction Steps: 5 1.1: dibenzoyl-L-(-)-tartaric acid / methanol / Heating 1.2: base 2.1: Et3N; DMAP / tetrahydrofuran / 6 h / 20 °C 3.1: 95 percent / H2 / Pd/C / methanol 4.1: 95 percent / cesium carbonate / dimethylformamide / 2 h 5.1: 98 percent / LiAlH4 / tetrahydrofuran / 2 h / Heating With 4-(N,N-dimethlyamino)pyridine, lithium aluminium tetrahydride, hydrogen, caesium carbonate, triethylamine, (2R,3S)-(-)-di-O-benzoyl tartaric acid, palladium on activated charcoal in tetrahydrofuran, methanol, N,N-dimethylformamide Pizarro, Nieves; De la Torre, Rafael; Farre, Magi; Segura, Jordi; Llebaria, Amadeu; Joglar, Jesus; Bioorganic and Medicinal Chemistry; vol. 10; nb. 4; (2002); p. 1085 - 1092

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View in Reaxys O N O

H N

Rx-ID: 14961279 View in Reaxys 58/67 Yield

Conditions & References Reaction Steps: 6 1.1: 71 percent / LiAlH4 / tetrahydrofuran / 4 h / Heating 2.1: dibenzoyl-L-(-)-tartaric acid / methanol / Heating 2.2: base 3.1: Et3N; DMAP / tetrahydrofuran / 6 h / 20 °C 4.1: 95 percent / H2 / Pd/C / methanol 5.1: 95 percent / cesium carbonate / dimethylformamide / 2 h 6.1: 98 percent / LiAlH4 / tetrahydrofuran / 2 h / Heating With 4-(N,N-dimethlyamino)pyridine, lithium aluminium tetrahydride, hydrogen, caesium carbonate, triethylamine, (2R,3S)-(-)-di-O-benzoyl tartaric acid, palladium on activated charcoal in tetrahydrofuran, methanol, N,N-dimethylformamide Pizarro, Nieves; De la Torre, Rafael; Farre, Magi; Segura, Jordi; Llebaria, Amadeu; Joglar, Jesus; Bioorganic and Medicinal Chemistry; vol. 10; nb. 4; (2002); p. 1085 - 1092 View in Reaxys

H N

N O

O O

Rx-ID: 4743870 View in Reaxys 59/67 Yield

Conditions & References With hydrogen, triethylamine, palladium on activated charcoal in ethanol, Time= 2h, Ambient temperature, Yield given Effenberger, Franz; Jaeger, Juergen; Chemistry - A European Journal; vol. 3; nb. 8; (1997); p. 1370 - 1374 View in Reaxys

O H 311C

H 11 3 C

H N

H 2N

Rx-ID: 4818733 View in Reaxys 60/67 Yield

Conditions & References in acetonitrile, Time= 0.333333h, T= 120 °C Solbach, M.; Guendisch, D.; Wuellner, U.; Blocher, A.; Kovar, K.-A.; Machulla, H.-J.; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 40; (1997); p. 522 - 524 View in Reaxys

H N

OH O O

H N

O O

Rx-ID: 17233407 View in Reaxys 61/67

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Yield

Conditions & References Reaction Steps: 2 1: 91 percent / Et3N / CH2Cl2; toluene / 0.5 h / Ambient temperature 2: Et3N, H2 / 10percent Pd/C / ethanol / 2 h / Ambient temperature With hydrogen, triethylamine, palladium on activated charcoal in ethanol, dichloromethane, toluene Effenberger, Franz; Jaeger, Juergen; Chemistry - A European Journal; vol. 3; nb. 8; (1997); p. 1370 - 1374 View in Reaxys

H N

Rx-ID: 3626751 View in Reaxys 62/67 Yield

Conditions & References With lithium aluminium tetrahydride in diethyl ether, Time= 4h, Heating, Yield given Nichols; Hoffman; Oberlender; Jacob III; Shulgin; Journal of Medicinal Chemistry; vol. 29; nb. 10; (1986); p. 2009 - 2015 View in Reaxys

H N

Rx-ID: 3626752 View in Reaxys 63/67 Yield

O H 2N

H N

O O

Rx-ID: 18834146 View in Reaxys 64/67 Yield

Conditions & References Reaction Steps: 2 1: Heating 2: LAH / diethyl ether / 4 h / Heating With lithium aluminium tetrahydride in diethyl ether Nichols; Hoffman; Oberlender; Jacob III; Shulgin; Journal of Medicinal Chemistry; vol. 29; nb. 10; (1986); p. 2009 - 2015 View in Reaxys

O H 2N

H N

O O

Rx-ID: 18834147 View in Reaxys 65/67 Yield

Conditions & References Reaction Steps: 2 1: Heating 2: LAH / diethyl ether / 4 h / Heating With lithium aluminium tetrahydride in diethyl ether

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Nichols; Hoffman; Oberlender; Jacob III; Shulgin; Journal of Medicinal Chemistry; vol. 29; nb. 10; (1986); p. 2009 - 2015 View in Reaxys H N

H 2N O

Rx-ID: 1835320 View in Reaxys 66/67 Yield

Conditions & References With sodium cyanoborohydride in methanol, Time= 36h, Ambient temperature, pH neutral (12N HCl) Braun; Shulgin; Journal of Pharmaceutical Sciences; vol. 69; nb. 2; (1980); p. 192 - 195 View in Reaxys

H N

O O

Rx-ID: 132179 View in Reaxys 67/67 Yield

Conditions & References With hydrogen bromide, T= 0 °C , Erhitzen des Reaktionsprodukts mit alkoh. Methylamin-Loesung auf 130grad Patent; Merck; DE274350; Fortschr. Teerfarbenfabr. Verw. Industriezweige; vol. 12; p. 768 View in Reaxys

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