tert-butyl 2-(aminomethyl)pyrrolidine-1-carboxylate

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

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

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

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

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

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

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

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

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

Procedure: To 2-aminomethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (1.00 g, 4.97 mmol) and 4-bromo-benzoic acid (996 mg, 4.97 mmol) in DMF (25 mL) was added N-methylmorpholine (655 μl, 5.96 mmol) and HATU (1.89 g, 4.97 mmol). After stirring for 3 hours the reaction was concentrated then diluted with EtOAc and washed with 1N HCl, saturated NaHCO3, and brine. The organic phase was then dried over Na2SO4 and concentrated. The crude material was purified by silica gel chromatography (20-50% EtOAc-hexanes gradient) to afford 2-[(4-bromo-benzoylamino)-methyl]-pyrrolidine-1-carboxylic acid tert-butyl ester (1.91 g, 4.97 mmol, quantitative yield). LCMS-ESI+: calc'd for C17H24BrN2O3: 383.1 (M+H+). Found: 383.6 (M+H+). was concentrated then diluted with EtOAc washed with 1N HCl, saturated NaHCO3, and brine The organic phase was then dried over Na2SO4 concentrated The crude material was purified by silica gel chromatography (20-50% EtOAc-hexanes gradient)

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

Procedure: (S)-Ethyl 2-((1-(tert-butoxycarbonyl)pyrrolidin-2-yl)methylamino)-6-(2-methoxy-phenylamino)-5-nitropyrimidine-4-carboxylate. Ethyl 2-chloro-6-(2-methoxyphenylamino)-5-nitropyrimidine-4-carboxylate (See Example 30.A) (0.300 g, 0.852 mmol), (S) 1-boc-(aminomethyl)pyrrolidine (0.206 g, 1.02 mmol) and diisopropylethylamine (0.164 g, 1.27 mmol.) were reacted according to General Procedure C, except at room temperature and in dimethylformamide (5 mL). The crude reaction mixture was condensed and purified using Biotage chromatography (0-100% ethyl acetate in hexanes) to afford the title compound (0.416 g, 95%). MS (ESI) m/z 517.3 [M+1]+. The crude reaction mixture condensed purified

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

Procedure: (R)-Ethyl 2-((1-(tert-butoxycarbonyl)pyrrolidin-2-yl)methylamino)-6-(2-methoxy-phenylamino)-5-nitropyrimidine-4-carboxylate. Ethyl 2-chloro-6-(2-methoxyphenylamino)-5-nitropyrimidine-4-carboxylate (See Example 30.A) (0.300 g, 0.852 mmol), (R) 1-boc-(aminomethyl)pyrrolidine (0.207 g, 1.02 mmol) and diisopropylethylamine (0.164 g, 1.27 mmol) were reacted according to General Procedure C, except at room temperature and in dimethylformamide (5 mL). The crude reaction mixture was condensed and purified using Biotage chromatography (0-100% ethyl acetate in hexanes) to afford the title compound (0.430 g, 97%). MS (ESI) m/z 517.5 [M+1]+. The crude reaction mixture condensed purified

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