methyl (2S)-2-amino-5-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoate

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

Procedure: 3-(2-Amino-6-chloropyrimidin-4-ylsulfanyl)propionic acid (211 mg, 0.903 mmol) obtained in Step 1 of Example 2-8 was dissolved in a mixture of dichloromethane (5.0 ml) and N,N-dimethylformamide (2.0 ml), and then 1-hydroxybenzotriazole monohydrate (139 mg, 0.887 mmol), (S)-2-amino-5-tert-butoxycarbonylaminopentanoic acid methyl ester (202 mg, 0.822 mmol), 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (173 mg, 0.902 mmol), and diisopropylethylamine (0.157 ml, 0.901 mmol) were added thereto. After the resulting mixture was stirred at room temperature for four hours, water (30 ml) was added to the reaction solution. The mixture was extracted three times with ethyl acetate (30 ml). The organic layers were combined together and then sequentially washed with a saturated aqueous sodium chloride solution (20 ml), a saturated aqueous sodium bicarbonate solution (20 ml), and a saturated aqueous sodium chloride solution (20 ml). The washed organic layer was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The resulting crude product was purified by silica gel column chromatography (developing solvent: dichloromethane:methanol=30:1) to yield (S)-2-[3-(2-amino-6-chloropyrimidin-4-ylsulfanyl)propionylamino]-5-tert-butoxycarbonylamino pentanoic acid methyl ester (359 mg) as a white amorphous material. The mixture was extracted three times with ethyl acetate (30 ml) sequentially washed with a saturated aqueous sodium chloride solution (20 ml) The washed organic layer was dried over anhydrous sodium sulfate After filtration the filtrate was concentrated under reduced pressure The resulting crude product was purified by silica gel column chromatography (developing solvent: dichloromethane:methanol=30:1)