Glycine, N-(phenylMethyl)-, Methyl ester

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: In scheme 6 b), methyl bromoacetate 22 is treated with benzylamine in CH2Cl2 at room temperature for 16 h. The N-benzylglycine methyl ester derivative 23 was obtained in 86% yield. This intermediate can be either acylated with a carboxylic acid derivative and DCC in THF or sulfonated with an appropriate sulfonyl chloride and triethylamine in CH2Cl2 to give derivative 24 or 25 as desired in good to excellent yields.

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

Procedure: Using the method of Example 39, the product from Example 38 was reacted with methanol and N-benzylglycine methyl ester to give the title compound.

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

Procedure: Methyl 6-chloro-5-nitronicotinate (2.0 g, 9.23 mmol) was added to methyl 2-(benzylamino)acetate (6.0 g, 31.05 mmol) neat while stirring at room temperature. The viscous yellow reaction was heated to 90° C. for one h and then allowed to cool back to room temperature. The reaction was diluted with dichloromethane (20 mL) and purified via column chromatography (220 g SiO2, 20-30% gradient, ethyl acetate in hexanes) to yield the title compound (3.10 g, 90% yield) as a yellow oil. [M+H] calc'd for C18H19N3O6, 374. found, 374. The viscous yellow reaction was heated to 90° C. for one h to cool back to room temperature purified via column chromatography (220 g SiO2, 20-30% gradient, ethyl acetate in hexanes)

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

Procedure: To a solution of methyl 2-(benzylamino)acetate (21.30 g, 119.2 mmol, 1.0 eq) in DMF (150 mL) was added anhydrous K2CO3 (8.02 g, 143.02 mmol, 1.2 eq) followed by allyl bromide (12.37 mL, 143.02 mmol, 1.2 eq) at room temperature. The mixture was stirred for 4 h, quenched with water and extracted with EtOAc (100 mL×3). The combined organic phases were washed with water and brine, dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by a silica gel column chromatography (20:1 (v/v) PE/EtOAc) to afford the title compound as colorless oil (18.30 g, 70%). The compound was characterized by the following spectroscopic data: 1H NMR (400 MHz, CDCl3) δ: 3.27 (2H, d, J=6.4 Hz), 3.32 (2H, s), 3.68 (3H, s), 3.78 (2H, s), 5.19 (2H, m), 5.88 (1H, m), 7.23-7.35 (5H, m) ppm. quenched with water extracted with EtOAc (100 mL×3) The combined organic phases were washed with water and brine dried over anhydrous Na2SO4 concentrated in vacuo The residue was purified by a silica gel column chromatography (20:1 (v/v) PE/EtOAc)

Conditions: temp:-5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of methyl 2-aminoacetate hydrochloride (15.00 g, 116.00 mmol, 1.0 eq) in CH2Cl2 (150 mL) was added Et3N (20 mL, 143.3 mmol, 1.2 eq) and PhCHO (14.6 mL, 143.3 mmol, 1.2 eq) in turn. The reaction mixture was stirred at room temperature overnight, and concentrated in vacuo. The residue was diluted with EtOAc and filtered. The filtrate was concentrated in vacuo to afford the crude product methyl 2-(benzylideneamino)acetate, which was used for the next step without further purification. To a solution of methyl 2-(benzylideneamino)acetate in MeOH (200 mL) at −5° C. was added NaBH4 (2.80 g, 72.8 mmol, 0.55 eq) slowly. The reaction mixture was stirred at −5° C. for 2 h. The reaction mixture was then quenched with water and extracted with EtOAc (100 mL×3). The combined organic phases were washed with water followed by brine, dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by a silica gel column chromatography (20:1 (v/v) PE/EtOAc) to afford the title compound as colorless oil (21.30 g, 99%). was used for the next step without further purification The reaction mixture was then quenched with water extracted with EtOAc (100 mL×3) The combined organic phases were washed with water dried over anhydrous Na2SO4 concentrated in vacuo The residue was purified by a silica gel column chromatography (20:1 (v/v) PE/EtOAc)

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

Procedure: In scheme 6b), methyl bromoacetate 22 is treated with benzylamine in CH2Cl2 at room temperature for 16 h. The N-benzylglycine methyl ester derivative 23 was obtained in 86% yield. This intermediate can be either acylated with a carboxylic acid derivative and DCC in THF or sulfonated with an appropriate sulfonyl chloride and triethylamine in CH2Cl2 to give derivative 24 or 25 as desired in good to excellent yields.

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

Procedure: In scheme 6 b), methyl bromoacetate 22 is treated with benzylamine in CH2Cl2 at room temperature for 16 h. The N-benzylglycine methyl ester derivative 23 was obtained in 86% yield. This intermediate can be either acylated with a carboxylic acid derivative and DCC in THF or sulfonated with an appropriate sulfonyl chloride and triethylamine in CH2Cl2 to give derivative 24 or 25 as desired in good to excellent yields.

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

Procedure: In scheme 6 b), methyl bromoacetate 22 is treated with benzylamine in CH2Cl2 at room temperature for 16 h. The N-benzylglycine methyl ester derivative 23 was obtained in 86% yield. This intermediate can be either acylated with a carboxylic acid derivative and DCC in THF or sulfonated with an appropriate sulfonyl chloride and triethylamine in CH2Cl2 to give derivative 24 or 25 as desired in good to excellent yields.

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: Methyl 6-chloro-5-nitronicotinate (2.0 g, 9.23 mmol) was added to methyl 2-(benzylamino)acetate (6.0 g, 31.05 mmol) neat while stirring at room temperature. The viscous yellow reaction was heated to 90° C. for one h and then allowed to cool back to room temperature. The reaction was diluted with dichloromethane (20 mL) and purified via column chromatography (220 g SiO2, 20-30% gradient, ethyl acetate in hexanes) to yield the title compound (3.10 g, 90% yield) as a yellow oil. [M+H] calc'd for C, 18; H, 19; N, 3O, 6, 374; found, 374. The viscous yellow reaction was heated to 90° C. for one h to cool back to room temperature purified via column chromatography (220 g SiO2, 20-30% gradient, ethyl acetate in hexanes)