methyl 2-(cyclopentylamino)acetate

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

Procedure: Triethylamine (10.9 mL, 78.2 mmol) was added to a solution of compound 224 (12.3 g, 65.2 mmol) and compound 225 (12.8 g, 81.5 mmol) in THF (200 mL). The reaction was stirred at room temperature. After 6 h, the reaction contents were poured into saturated sodium bicarbonate and extracted with ethyl acetate. The combined organics were dried over MgSO4 and concentrated in vacuo. The crude material was crystallized from ethyl acetate and hexanes to afford methyl 2-(cyclopentyl(5-formyl-2-(methylthio)pyrimidin-4-yl)amino)acetate (226) (17.55 g, 87.0% yield). the reaction contents extracted with ethyl acetate The combined organics were dried over MgSO4 concentrated in vacuo The crude material was crystallized from ethyl acetate and hexanes

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

Procedure: A solution of methyl bromoacetate (17.4 mL, 188 mmol) in THF (40 mL) was dropwise added to a solution of cyclopentylamine (18.6 mL, 188 mmol) and triethylamine (26.1 mL, 188 mmol) in THF (150 mL) at 0° C. Following addition, the reaction was allowed to reach room temperature and was stirred overnight. The triethylammonium salts were filtered and rinsed with scant THF. The combined filtrates were concentrated in vacuo. The desired product was distilled from the residuals under reduced pressure to yield 20.2 g of compound 225 (68% yield). 1H NMR (500 MHz, CDCl3) δ ppm 3.73 (s, 3 H) 3.41 (s, 2 H) 3.00-3.13 (m, J=12.90, 6.39, 6.39 Hz, 1 H) 1.77-1.87 (m, 2 H) 1.67-1.74 (m, 2 H) 1.48-1.59 (m, 2 H) 1.29-1.41 (m, 2 H) ppm. addition to reach room temperature The triethylammonium salts were filtered rinsed with scant THF The combined filtrates were concentrated in vacuo The desired product was distilled from the residuals under reduced pressure

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

Procedure: A solution of methyl bromoacetate (17.4 mL, 188 mmol) in THF (40 mL) was dropwise added to a solution of cyclopentylamine (18.6 mL, 188 mmol) and triethylamine (26.1 mL, 188 mmol) in THF (150 mL) at 0° C. Following addition, the reaction was allowed to reach room temperature and was stirred overnight. The triethylammonium salts were filtered and rinsed with scant THF. The combined filtrates were concentrated in vacuo. The desired product was distilled from the residuals under reduced pressure to yield 20.2 g of compound 225 (68% yield). 1H NMR (500 MHz, CDCl3) δ ppm 3.73 (s, 3 H) 3.41 (s, 2 H) 3.00-3.13 (m, J=12.90, 6.39, 6.39 Hz, 1 H) 1.77-1.87 (m, 2 H) 1.67-1.74 (m, 2 H) 1.48-1.59 (m, 2 H) 1.29-1.41 (m, 2 H) ppm. addition to reach room temperature The triethylammonium salts were filtered rinsed with scant THF The combined filtrates were concentrated in vacuo The desired product was distilled from the residuals under reduced pressure

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

Procedure: Triethylamine (10.9 mL, 78.2 mmol) was added to a solution of compound 224 (12.3 g, 65.2 mmol) and compound 225 (12.8 g, 81.5 mmol) in THF (200 mL). The reaction was stirred at room temperature. After 6 h, the reaction contents were poured into saturated sodium bicarbonate and extracted with ethyl acetate. The combined organics were dried over MgSO4 and concentrated in vacuo. The crude material was crystallized from ethyl acetate and hexanes to afford methyl 2-(cyclopentyl(5-formyl-2-(methylthio)pyrimidin-4-yl)amino)acetate (226) (17.55 g, 87.0% yield). the reaction contents extracted with ethyl acetate The combined organics were dried over MgSO4 concentrated in vacuo The crude material was crystallized from ethyl acetate and hexanes

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

Procedure: A solution of methyl bromoacetate (17.4 mL, 188 mmol) in THF (40 mL) was dropwise added to a solution of cyclopentylamine (18.6 mL, 188 mmol) and triethylamine (26.1 mL, 188 mmol) in THF (150 mL) at 0° C. Following addition, the reaction was allowed to reach room temperature and was stirred overnight. The triethylammonium salts were filtered and rinsed with scant THF. The combined filtrates were concentrated in vacuo. The desired product was distilled from the residuals under reduced pressure to yield 20.2 g of compound 225 (68% yield). 1H NMR (500 MHz, CDCl3) δ ppm 3.73 (s, 3 H) 3.41 (s, 2 H) 3.00-3.13 (m, J=12.90, 6.39, 6.39 Hz, 1 H) 1.77-1.87 (m, 2 H), 1.67-1.74 (m, 2 H) 1.48-1.59 (m, 2 H) 1.29-1.41 (m, 2 H) ppm. addition to reach room temperature The triethylammonium salts were filtered rinsed with scant THF The combined filtrates were concentrated in vacuo The desired product was distilled from the residuals under reduced pressure

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

Procedure: Triethylamine (10.9 mL, 78.2 mmol) was added to a solution of compound 224 (12.3 g, 65.2 mmol) and compound 225 (12.8 g, 81.5 mmol) in THF (200 mL). The reaction was stirred at room temperature. After 6 h, the reaction contents were poured into saturated sodium bicarbonate and extracted with ethyl acetate. The combined organics were dried over MgSO4 and concentrated in vacuo. The crude material was crystallized from ethyl acetate and hexanes to afford methyl 2-(cyclopentyl(5-formyl-2-(methylthio)pyrimidin-4-yl)amino)acetate (226) (17.55 g, 87.0% yield). the reaction contents extracted with ethyl acetate The combined organics were dried over MgSO4 concentrated in vacuo The crude material was crystallized from ethyl acetate and hexanes

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

Procedure: A solution of methyl bromoacetate (17.4 mL, 188 mmol) in THF (40 mL) was dropwise added to a solution of cyclopentylamine (18.6 mL, 188 mmol) and triethylamine (26.1 mL, 188 mmol) in THF (150 mL) at 0° C. Following addition, the reaction was allowed to reach room temperature and was stirred overnight. The triethylammonium salts were filtered and rinsed with scant THF. The combined filtrates were concentrated in vacuo. The desired product was distilled from the residuals under reduced pressure to yield 20.2 g of compound 225 (68% yield). 1H NMR (500 MHz, CDCl3) δ ppm 3.73 (s, 3 H) 3.41 (s, 2 H) 3.00-3.13 (m, J=12.90, 6.39, 6.39 Hz, 1 H) 1.77-1.87 (m, 2 H) 1.67-1.74 (m, 2 H) 1.48-1.59 (m, 2 H) 1.29-1.41 (m, 2 H) ppm. addition to reach room temperature The triethylammonium salts were filtered rinsed with scant THF The combined filtrates were concentrated in vacuo The desired product was distilled from the residuals under reduced pressure