* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
With hydrogen;palladium on activated charcoal; In methanol; for 18.0h;
5-Amino-1-methylindolin-2-one; To a suspension of l-methyl-5-nitroindolin-2-one (92 mg, 0.48 mmol) in 20 mL MeOH, was Pd(C) (9.2 mg, 10 weight %) added. The round bottom flask was capped with a rubber septum and put under a hydrogen atmosphere. After 18 h the hydrogen gas was evacuated by introducing argon to the round bottom flask. The reaction mixture was filtered through celite. The celite was washed with EtOAc (2X 30 ml). The volatiles were evaporated to afford the title compound in quantitative yield.
With iron; ammonium chloride; In ethanol; water; at 20 - 90℃; for 0.5h;
Step 3: Preparation of 5-amino-1-methyl-1,3-dihydro-indol-2-one Iron powder (2.09 g, 37.46 mmol) is added in small portion to a mixture of 1-methyl-5-nitro-1,3-dihydro-indol-2-one (Step 2, 1.8 g, 9.36 mmol) and ammonium chloride (4.96 g, 93.6 mmol) in ethanol (100 ml) and water (50 ml) at 90 C. The reaction mixture is stirred vigorously and heated for 30 min, cooled to room temperature, and diluted with dichloromethane (200 ml). The mixture is filtered through celite, the organic layer separated and washed with water and brine, dried over sodium sulfate, and evaporated to give the title compound as a dark brown solid. HPLC r.t. 1.06 min; MS for C9H10N2O Mn/Z 163.2(M+H)+.
With iron; ammonium chloride; In ethanol; water; at 90℃; for 0.5h;
Step 3; Preparation of 5-amino-1-methyl-1,3-dihydro-indol-2-one; Iron powder (2.09 g, 37.46 mmol) is added in small portion to a mixture of 1-methyl-5-nitro-1,3-dihydro-indol-2-one (Step 2, 1.8 g, 9.36 mmol) and ammonium chloride (4.96 g, 93.6 mmol) in ethanol (100 ml) and water (50 ml) at 90 C. The reaction mixture is stirred vigorously and heated for 30 min, cooled to room temperature, and diluted with dichloromethane (200 ml). The mixture is filtered through celite, the organic layer separated and washed with water and brine, dried over sodium sulfate, and evaporated to give the title compound as a dark brown solid. HPLC r.t. 1.06 min; MS for C9H10N2O m/z 163.2(M+H)+.
With lithium trifluoromethanesulfonate; In acetonitrile; at 70℃; for 4.0h;
Step 4: Preparation of (5R)-2-hydroxy-3-(1-methyl-2-oxo-2,3-dihydro-1H-indol-5-ylamino)-propionic acid methyl ester 5-Amino-1-methyl-1,3-dihydro-indol-2-one (Step 3, 1.40 g, 8.63 mmol), methyl (2R)-glycidate (0.882 g, 8.63 mmol), and lithium trifluoromethanesulfonate (1.33 g, 8.63 mmol) in acetonitrile (15 ml) are heated at 70 C. for 4 hours. The reaction mixture is diluted with ethyl acetate, washed with water and brine, dried (Na2SO4) and evaporated. The residue is purified by flash chromatography (70% EtOAc/Hexane) to give the title compound as a light brown solid. HPLC r.t. 2.44 min; MS for C13H16N2O4 m/z 265.0(M+H)+.
With lithium trifluoromethanesulfonate; In acetonitrile; at 70℃; for 1.0h;
Step 4; Preparation of (R)-[2-hydroxy-3-(1-methyl-2-oxo-2,3-dihydro-1H-indol-5-ylamino)-propyl]-carbamic acid tert-butyl ester; 5-Amino-1-methyl-1,3-dihydro-indol-2-one (1.20 g, 7.40 mmol), (S)-oxiranylmethyl-carbamic acid tert-butyl ester (1.28 g, 7.40 mmol) and lithium trifluoromethanesulfonate (1.14 g, 7.398 mmol) in acetonitrile (10 ml) are heated at 70 C. for 1 hour. The reaction mixture is diluted with ethyl acetate, washed with water and brine, dried (Na2SO4) and evaporated. The residue is purified by flash column chromatography (70% EtOAc/Hexane) to give the title compound as a light brown solid. HPLC r.t. 3.20 min; MS for C17H25N3O4 m/z 336.4(M+H)+.