1-(4-benzylmorpholin-2-yl)-N-methylmethanamine

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Quinolinone I was synthesized from commercially available 2-chloromethyl-4-benzyl morpholine, methylamine, 4-chloro-2-nitroaniline, and 2-amino-6-fluorobenzonitrile following the general procedure of Example 49. (2-(methylamino)methyl-4-benzyl morpholine was dissolved in an 8 M solution of NH2Me in EtOH and heated in a glass bomb at 110° C. overnight to form the product 2-(methylamino)methyl-4-benzyl morpholine following removal of the solvent). Compound I (1.0 equivalent) and 10% Pd/C (0.1 equivalents) were suspended in 1:1 ethanol and 1 N aqueous HCl at room temperature. The reaction flask was evacuated and subsequently filled with H2. The resulting mixture was stirred under a hydrogen atmosphere overnight, filtered through Celite, and concentrated under vacuum. The solution was made basic with 30% aq. KOH and the product was extracted with EtOAc. The combined organic layers were concentrated and resuspended in CH2Cl2:MeOH:AcOH (2:2:1). Paraformaldehyde (1.2 equivalents) and BH3 pyridine (3 equivalents, 8 M) was then added and the mixture was stirred overnight at room temperature. The solvent was removed in vacuo and washed with water. The aqueous layer was extracted with EtOAc (3×), and the combined organic layers were concentrated and purified by silica gel chromatography (10% MeOH/CH2Cl2) to afford the desired product. MH+=437.4. to form the product 2-(methylamino)methyl-4-benzyl morpholine following removal of the solvent) The reaction flask was evacuated subsequently filled with H2 filtered through Celite concentrated under vacuum the product was extracted with EtOAc The combined organic layers were concentrated the mixture was stirred overnight at room temperature The solvent was removed in vacuo washed with water The aqueous layer was extracted with EtOAc (3×) the combined organic layers were concentrated purified by silica gel chromatography (10% MeOH/CH2Cl2)

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Quinolinone I was synthesized from commercially available 2-chloromethyl-4-benzyl morpholine, methylamine, 4-chloro-2-nitroaniline, and 2-amino-6-fluorobenzonitrile following the general procedure of Example 49. (2-(methylamino)methyl-4-benzyl morpholine was dissolved in an 8 M solution of NH2Me in EtOH and heated in a glass bomb at 110° C. overnight to form the product 2-(methylamino)methyl-4-benzyl morpholine following removal of the solvent). Compound I (1.0 equivalent) and 10% Pd/C (0.1 equivalents) were suspended in 1:1 ethanol and 1 N aqueous HCl at room temperature. The reaction flask was evacuated and subsequently filled with H2. The resulting mixture was stirred under a hydrogen atmosphere overnight, filtered through Celite, and concentrated under vacuum. The solution was made basic with 30% aq. KOH and the product was extracted with EtOAc. The combined organic layers were concentrated and resuspended in CH2Cl2:MeOH:AcOH (2:2:1). Paraformaldehyde (1.2 equivalents) and BH3 pyridine (3 equivalents, 8 M) was then added and the mixture was stirred overnight at room temperature. The solvent was removed in vacuo and washed with water. The aqueous layer was extracted with EtOAc (3×), and the combined organic layers were concentrated and purified by silica gel chromatography (10% MeOH/CH2Cl2) to afford the desired product. MH+=437.4. to form the product 2-(methylamino)methyl-4-benzyl morpholine following removal of the solvent) The reaction flask was evacuated subsequently filled with H2 filtered through Celite concentrated under vacuum the product was extracted with EtOAc The combined organic layers were concentrated the mixture was stirred overnight at room temperature The solvent was removed in vacuo washed with water The aqueous layer was extracted with EtOAc (3×) the combined organic layers were concentrated purified by silica gel chromatography (10% MeOH/CH2Cl2)

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Commercially available 2-chloromethyl-4-benzyl morpholine was dissolved in an 8 M solution of NH2Me in EtOH and heated in a glass pressure vessel at 110° C. overnight. The solvent was removed in vacuo, and the compound was used in the next step without further purification. LC/MS m/z: 221.2 (MH+), Rt 0.55 minutes. The solvent was removed in vacuo the compound was used in the next step without further purification

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Quinolinone I was synthesized from commercially available 2-chloromethyl-4-benzyl morpholine, methylamine, 4-chloro-2-nitroaniline, and 2-amino-6-fluorobenzonitrile following the general procedure of Example 49. (2-(methylamino)methyl-4-benzyl morpholine was dissolved in an 8 M solution of NH2Me in EtOH and heated in a glass bomb at 110° C. overnight to form the product 2-(methylamino)methyl-4-benzyl morpholine following removal of the solvent). Compound I (1.0 equivalent) and 10% Pd/C (0.1 equivalents) were suspended in 1:1 ethanol and 1 N aqueous HCl at room temperature. The reaction flask was evacuated and subsequently filled with H2. The resulting mixture was stirred under a hydrogen atmosphere overnight, filtered through Celite, and concentrated under vacuum. The solution was made basic with 30% aq. KOH and the product was extracted with EtOAc. The combined organic layers were concentrated and resuspended in CH2Cl2:MeOH:AcOH (2:2:1). Paraformaldehyde (1.2 equivalents) and BH3.pyridine (3 equivalents, 8 M) was then added and the mixture was stirred overnight at room temperature. The solvent was removed in vacuo and washed with water. The aqueous layer was extracted with EtOAc (3×), and the combined organic layers were concentrated and purified by silica gel chromatography (10% MeOH/CH2Cl2) to afford the desired product. MH+=437.4. to form the product 2-(methylamino)methyl-4-benzyl morpholine following removal of the solvent) The reaction flask was evacuated subsequently filled with H2 filtered through Celite concentrated under vacuum the product was extracted with EtOAc The combined organic layers were concentrated the mixture was stirred overnight at room temperature The solvent was removed in vacuo washed with water The aqueous layer was extracted with EtOAc (3×) the combined organic layers were concentrated purified by silica gel chromatography (10% MeOH/CH2Cl2)

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Commercially available 2-chloromethyl-4-benzyl morpholine was dissolved in an 8 M solution of NH2Me in EtOH and heated in a glass pressure vessel at 110° C. overnight. The solvent was removed in vacuo, and the compound was used in the next step without further purification. LC/MS m/z: 221.2 (MH+), Rt 0.55 minutes. The solvent was removed in vacuo the compound was used in the next step without further purification