N-BOC-N'-甲基硫脲

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Starting from (S)-3-amino-3-(5-bromo-2-fluoro-phenyl)-2,2-dimethyl-butyric acid methyl ester and tert-butyl [(methylamino)carbonothioyl]carbamate, the product [(S)-4-(5-bromo-2-fluoro-phenyl)-1,4,5,5-tetramethyl-6-oxo-1,4,5,6-tetrahydro-pyrimidin-2-yl]-carbamic acid tert-butyl ester was obtained as a white solid. MS (ESI): m/z=442.2 and 444.1 [M+H]+.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Starting from (S)-3-amino-3-(2-fluoro-phenyl)-2,2-dimethyl-butyric acid methyl ester and tert-butyl [(methylamino)carbonothioyl]carbamate, the product [(S)-4-(2-fluoro-phenyl)-1,4,5,5-tetramethyl-6-oxo-1,4,5,6-tetrahydro-pyrimidin-2-yl]-carbamic acid tert-butyl ester was obtained as a white solid. MS (ESI): m/z=364.2 [M+H]+.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Starting from (S)-3-amino-3-(2-fluoro-phenyl)-2,2-dimethyl-butyric acid methyl ester and tert-butyl [(methylamino)carbonothioyl]carbamate, the product [(S)-4-(2-fluoro-phenyl)-1,4,5,5-tetramethyl-6-oxo-1,4,5,6-tetrahydro-pyrimidin-2-yl]-carbamic acid tert-butyl ester was obtained as a white solid. MS (ESI): m/z=364.2 [M+H]+.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Starting from ((S)-1-amino-6-nitro-indan-1-yl)-acetic acid methyl ester and tert-butyl [(methylamino)carbonothioyl]carbamate, the product tert-butyl [(1S)-1′-methyl-6-nitro-6′-oxo-2,3,5′,6′-tetrahydro-1′H-spiro[indene-1,4′-pyrimidin]-2′-yl]carbamate was obtained as pale brown solid. MS (ESI): m/z=373.1 [M−H]−.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Starting from ((S)-1-amino-6-nitro-indan-1-yl)-acetic acid methyl ester and tert-butyl [(methylamino)carbonothioyl]carbamate, the product tert-butyl [(1S)-1′-methyl-6-nitro-6′-oxo-2,3,5′,6′-tetrahydro-1′H-spiro[indene-1,4′-pyrimidin]-2′-yl]carbamate was obtained as pale brown solid. MS (ESI): m/z=373.1 [M−H]−.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Starting from (S)-3-amino-3-(3-nitro-phenyl)-hexanoic acid methyl ester and tert-butyl [(methylamino)carbonothioyl]carbamate, the product [(S)-1-methyl-4-(3-nitro-phenyl)-6-oxo-4-propyl-1,4,5,6-tetrahydro-pyrimidin-2-yl]-carbamic acid tert-butyl ester was obtained as an amorphous solid. MS (ESI): m/z=389.3 [M−H]−.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Starting from (S)-3-amino-3-(3-nitro-phenyl)-butyric acid methyl ester and tert-butyl [(methylamino)carbonothioyl]carbamate, the product [(S)-1,4-dimethyl-4-(3-nitro-phenyl)-6-oxo-1,4,5,6-tetrahydro-pyrimidin-2-yl]-carbamic acid tert-butyl ester was obtained as white solid. MS (ESI): m/z=361.4 [M−H]−.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Starting from (S)-3-amino-3-(3-nitro-phenyl)-butyric acid methyl ester and tert-butyl [(methylamino)carbonothioyl]carbamate, the product [(S)-1,4-dimethyl-4-(3-nitro-phenyl)-6-oxo-1,4,5,6-tetrahydro-pyrimidin-2-yl]-carbamic acid tert-butyl ester was obtained as white solid. MS (ESI): m/z=361.4 [M−H]−.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Starting from (S)-3-amino-3-(2-fluoro-5-nitro-phenyl)-2,2-dimethyl-butyric acid methyl ester and tert-butyl [(methylamino)carbonothioyl]carbamate, the product [(S)-4-(2-fluoro-5-nitro-phenyl)-1,4,5,5-tetramethyl-6-oxo-1,4,5,6-tetrahydro-pyrimidin-2-yl]-carbamic acid tert-butyl ester was obtained as pale yellow oil. MS (ESI): m/z=407.3 [M−H]−.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Starting from (R)-3-amino-2,2-dimethyl-3-(3-nitro-phenyl)-butyric acid methyl ester and tert-butyl [(methylamino)carbonothioyl]carbamate, the product [(R)-1,4,5,5-tetramethyl-4-(3-nitro-phenyl)-6-oxo-1,4,5,6-tetrahydro-pyrimidin-2-yl]-carbamic acid tert-butyl ester was obtained as a white solid. MS (ESI): m/z=391.3 [M+H]+.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Starting from (R)-3-amino-2,2-dimethyl-3-(3-nitro-phenyl)-butyric acid methyl ester and tert-butyl [(methylamino)carbonothioyl]carbamate, the product [(R)-1,4,5,5-tetramethyl-4-(3-nitro-phenyl)-6-oxo-1,4,5,6-tetrahydro-pyrimidin-2-yl]-carbamic acid tert-butyl ester was obtained as a white solid. MS (ESI): m/z=391.3 [M+H]+.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: tert-Butyl (methylcarbamothioyl)carbamate (2.13 g, 11.2 mmol) was added to a stirred mixture of (2R,3S,4S)-methyl 4-amino-4-(2-fluorophenyl)-2-methyltetrahydrofuran-3-carboxylate (2.27 g, 9.0 mmol), N-ethyl-N-(propan-2-yl)propan-2-amine (3.9 mL, 22.4 mmol) and N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (1:1) (2.15 g, 11.2 mmol) in dry DMF (18 mL) at RT under nitrogen. The mixture was stirred at RT for 3 days, then partitioned between EtOAc (50 mL) and saturated aqueous NaHCO3 (50 mL) and water (50 mL). The aqueous layer was further extracted with EtOAc (2×50 mL). The combined extracts were dried (Na2SO4), filtered and evaporated. The residue was purified by column chromatography (normal phase, 100 g, Biotage SNAP cartridge KP-Sil, 50 mL per min, gradient 10% to 25% EtOAc in n-hexane) to give the title compound (3.15 g, colourless foam). 1H NMR (400 MHz, CDCl3) δ ppm 1.51 (d, J=6.06 Hz, 3H) 1.54 (s, 9H) 3.28 (s, 3H) 3.40 (dd, J=9.09, 2.02 Hz, 1H) 4.31 (d, J=10.11 Hz, 1H) 4.36-4.45 (m, 2H) 7.10-7.24 (m, 3H) 7.33-7.40 (m, 1H) 10.53 (br. s., 1H). partitioned between EtOAc (50 mL) and saturated aqueous NaHCO3 (50 mL) and water (50 mL) The aqueous layer was further extracted with EtOAc (2×50 mL) The combined extracts were dried (Na2SO4) filtered evaporated The residue was purified by column chromatography (normal phase, 100 g, Biotage SNAP cartridge KP-Sil, 50 mL per min, gradient 10% to 25% EtOAc in n-hexane)