3-morpholin-4-ylpropanehydrazide

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Prepared according to a procedure reported for related compounds: Henichart, J. P. et al. J. Het Chem. 1977, 14, 615. Methyl isothiocyanate (9.08 g, 0.124 mol) in EtOH (50 mL) was added at room temperature to a stirred solution of 3-morpholin-4-ylpropanohydrazide (21.5 g, 0.124 mol) in EtOH (200 mL). The mixture was refluxed for 8 h, then removed from heat and stirred at room temperature for 16 h. The EtOh was removed under reduced pressure to give the crude material as a yellow oil. The oil was purified by column chromatography through silica gel, eluting with CH2Cl2/MeOH to afford the title compound. (6 g, 21.2%). Prepared The mixture was refluxed for 8 h removed from heat The EtOh was removed under reduced pressure to give the crude material as a yellow oil The oil was purified by column chromatography through silica gel eluting with CH2Cl2/MeOH

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Hydrazine (64.1 g, 2 mol) was added dropwise, over 8–10 min, to methyl 3-morpholinopropionate (35 g, 0.202 mol) and the reaction mixture was refluxed for 16 h. The excess hydrazine was removed under reduced pressure and the material was dried in vacuo at room temperature for 16 h to give the crude product as an oil. The 1H NMR showed the presence of hydrazine, so the crude material was dried using a lyophilizer. Then the oil was refluxed in benzene/water (using a Dean-Stark distilling receiver). The benzene was then removed under reduced pressure, and the product was triturated with petroleum ether. After sitting in petroleum ether at room temperature for 16 h, the oil solidified. The petroleum ether was decanted and the solid was dried under house vacuum at room temperature to give the desired product (21.5 g, 61.4%), which was used without further purification. the reaction mixture was refluxed for 16 h The excess hydrazine was removed under reduced pressure the material was dried in vacuo at room temperature for 16 h to give the crude product as an oil so the crude material was dried Then the oil was refluxed in benzene/water ( distilling receiver) The benzene was then removed under reduced pressure the product was triturated with petroleum ether The petroleum ether was decanted the solid was dried under house vacuum at room temperature

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Prepared according to a procedure reported for related compounds: Henichart, J. P. et al. J. Het Chem. 1977, 14, 615. Methyl isothiocyanate (9.08 g, 0.124 mol) in EtOH (50 mL) was added at room temperature to a stirred solution of 3-morpholin-4-ylpropanohydrazide (21.5 g, 0.124 mol) in EtOH (200 mL). The mixture was refluxed for 8 h, then removed from heat and stirred at room temperature for 16 h. The EtOh was removed under reduced pressure to give the crude material as a yellow oil. The oil was purified by column chromatography through silica gel, eluting with CH2Cl2/MeOH to afford the title compound. (6 g, 21.2%) 1H NMR (DMSO-d6) d 2.42 (m, 4H) 2.64 (m, 2H) 2.85 (m, 2H, 3.43 (s, 3H) 3.55 (m, 4H) 13.47 (s, 1H). MS (APCI) calcd for C9H16N4OS: 228.32; found (M−H+) 227.1. Prepared The mixture was refluxed for 8 h removed from heat The EtOh was removed under reduced pressure to give the crude material as a yellow oil The oil was purified by column chromatography through silica gel eluting with CH2Cl2/MeOH

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Hydrazine (64.1 g, 2 mol) was added dropwise, over 8-10 min, to methyl 3-morpholinopropionate (35 g, 0.202 mol) and the reaction mixture was refluxed for 16 h. The excess hydrazine was removed under reduced pressure and the material was dried in vacuo at room temperature for 16 h to give the crude product as an oil. The 1H NMR showed the presence of hydrazine, so the crude material was dried using a lyophilizer. Then the oil was refluxed in benzene/water (using a Dean-Stark distilling receiver). The benzene was then removed under reduced pressure, and the product was triturated with petroleum ether. After sitting in petroleum ether at room temperature for 16 h, the oil solidified. The petroleum ether was decanted and the solid was dried under house vacuum at room temperature to give the desired product (21.5 g, 61.4%), which was used without further purification. the reaction mixture was refluxed for 16 h The excess hydrazine was removed under reduced pressure the material was dried in vacuo at room temperature for 16 h to give the crude product as an oil so the crude material was dried Then the oil was refluxed in benzene/water ( distilling receiver) The benzene was then removed under reduced pressure the product was triturated with petroleum ether The petroleum ether was decanted the solid was dried under house vacuum at room temperature

Conditions: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 106 mg (0.2 mmol) (RS)-1-(3,5-bis-trifluoromethyl-benzyl)-3-(3,4-dichloro-benzyl)-5-thioxo-[1,4]diazepan-2-one in 1 ml of butan-1-ol 42 mg (0.24 mmol) of 3-morpholin-4-yl-propionic acid hydrazide was added. The reaction mixture was stirred at 130° C. overnight. After evaporation of the solvent in vacuum water (5 ml) was added and the mixture was extracted three times with ethyl acetate. The combined organic layers are dried (MgSO4) and concentrated. The residue was purified by column chromatography (SiO2, dichloromethane/methanol=95:5) to yield 77 mg (59.2%) of the title compound as a light yellow solid. MS m/e (%): 650.0 (M+H+, 100). After evaporation of the solvent in vacuum water (5 ml) was added the mixture was extracted three times with ethyl acetate The combined organic layers are dried (MgSO4) concentrated The residue was purified by column chromatography (SiO2, dichloromethane/methanol=95:5)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Prepared according to a procedure reported for related compounds: Henichart, J. P. et al. J. Het Chem. 1977, 14, 615. Methyl isothiocyanate (9.08 g, 0.124 mol) in EtOH (50 mL) was added at room temperature to a stirred solution of 3-morpholin-4-ylpropanohydrazide (21.5 g, 0.124 mol) in EtOH (200 mL). The mixture was refluxed for 8 h, then removed from heat and stirred at room temperature for 16 h. The EtOh was removed under reduced pressure to give the crude material as a yellow oil. The oil was purified by column chromatography through silica gel, eluting with CH2Cl2/MeOH to afford the title compound. (6 g, 21.2%). Prepared The mixture was refluxed for 8 h removed from heat The EtOh was removed under reduced pressure to give the crude material as a yellow oil The oil was purified by column chromatography through silica gel eluting with CH2Cl2/MeOH

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Hydrazine (64.1 g, 2 mol) was added dropwise, over 8–10 min, to methyl 3-morpholinopropionate (35 g, 0.202 mol) and the reaction mixture was refluxed for 16 h. The excess hydrazine was removed under reduced pressure and the material was dried in vacuo at room temperature for 16 h to give the crude product as an oil. The 1H NMR showed the presence of hydrazine, so the crude material was dried using a lyophilizer. Then the oil was refluxed in benzene/water (using a Dean-Stark distilling receiver). The benzene was then removed under reduced pressure, and the product was triturated with petroleum ether. After sitting in petroleum ether at room temperature for 16 h, the oil solidified. The petroleum ether was decanted and the solid was dried under house vacuum at room temperature to give the desired product (21.5 g, 61.4%), which was used without further purification. the reaction mixture was refluxed for 16 h The excess hydrazine was removed under reduced pressure the material was dried in vacuo at room temperature for 16 h to give the crude product as an oil so the crude material was dried Then the oil was refluxed in benzene/water ( distilling receiver) The benzene was then removed under reduced pressure the product was triturated with petroleum ether The petroleum ether was decanted the solid was dried under house vacuum at room temperature