tert-butyl N-[[(2S)-oxiran-2-yl]methyl]carbamate

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a slurry of [3-fluoro-4(4-morpholinyl)phenyl]carbamic acid phenylmethyl ester (Example 1) (1.0039 g, 3.039 mmol) and tert-butyl (2S)oxiranylmethylcarbamate (Example 5) (0.653 g, 3.77 mmol, 1.24 eq) in THF (1.5 ml) at 0° C. was added a solution of lithium t-butoxide in THF (18.07 wt %, 1.735 g, 3.92 mmol, 1.29 eq). After standing 2 days at 20–25° C., methylene chloride (5.0 ml), then acetic acid (0.35 ml, 6.11 mmol, 2.01 eq) followed by water (3.5 ml) was added. The phases were separated and the aqueous washed with methylene chloride (3.5 ml). The combined organics were dried on magnesium sulfate and concentrated to an oil which was shown to contain 1.03 g (85.7%) of Compound III, wherein R1=3-fluoro-4-(4-morpholinyl)phenyl, R3=t-butyl, by external standard HPLC: retention time=4.06 min (column=Zorbax SB-C8 3.5 micron 150×4.6 mm, flow rate=2.0 ml/min, gradient elution from 30:70 A:B to 90:10 A:B over 15 minutes; A=969:30:1 acetonitrile: THF: trifluoroacetic acid; B=949:50:1 water: THF:trifluroracetic acid). was added The phases were separated the aqueous washed with methylene chloride (3.5 ml) The combined organics were dried on magnesium sulfate concentrated to an oil which 3.5 micron 150×4.6 mm, flow rate=2.0 ml/min, gradient elution from 30:70 A:B to 90:10 A:B over 15 minutes

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a slurry of [3-fluoro-4(4-morpholinyl)phenyl]carbamic acid phenylmethyl ester (Example 1) (1.0039 g, 3.039 mmol) and tert-butyl (2S)oxiranylmethylcarbamate (Example 5) (0.653 g, 3.77 mmol, 1.24 eq) in THF (1.5 ml) at 0° C. was added a solution of lithium t-butoxide in THF (18.07 wt %, 1.735 g, 3.92 mmol, 1.29 eq). After standing 2 days at 20–25° C., methylene chloride (5.0 ml), then acetic acid (0.35 ml, 6.11 mmol, 2.01 eq) followed by water (3.5 ml) was added. The phases were separated and the aqueous washed with methylene chloride (3.5 ml). The combined organics were dried on magnesium sulfate and concentrated to an oil which was shown to contain 1.03 g (85.7%) of Compound III, wherein R1=3-fluoro-4-(4-morpholinyl)phenyl, R3=t-butyl, by external standard HPLC: retention time=4.06 min (column=Zorbax SB-C8 3.5 micron 150×4.6 mm, flow rate=2.0 ml/min, gradient elution from 30:70 A:B to 90:10 A:B over 15 minutes; A=969:30:1 acetonitrile: THF: trifluoroacetic acid; B=949:50:1 water: THF:trifluroracetic acid). was added The phases were separated the aqueous washed with methylene chloride (3.5 ml) The combined organics were dried on magnesium sulfate concentrated to an oil which 3.5 micron 150×4.6 mm, flow rate=2.0 ml/min, gradient elution from 30:70 A:B to 90:10 A:B over 15 minutes

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 5-Amino-1-cyclopropylmethyl-7-fluoro-1,3-dihydro-indol-2-one (1.00 g, 4.55 mmol), (S)-oxiranylmethyl-carbamic acid tert-butyl ester (0.79 g, 4.55 mmol) and lithium trifluoromethanesulfonate (0.618 g, 4.55 mmol) in acetonitrile (20 ml) are heated at 90° C. for 16 hours. The reaction mixture is diluted with ethyl acetate, washed with water and brine, dried (Na2SO4) and evaporated. Final purification by flash chromatography (70% ethyl acetate/hexane) gives the title compound as a white solid. HPLC r.t. 4.35 min; MS for C20H28FN3O4 m/z 394.1 (M+H)+. washed with water and brine dried (Na2SO4) evaporated Final purification by flash chromatography (70% ethyl acetate/hexane)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 5-Amino-1-cyclopropyl-7-fluoro-1,3-dihydro-indol-2-one (0.560 g, 2.72 mmol), (S)-oxiranylmethyl-carbamic acid tert-butyl ester (0.472 g, 2.72 mmol) and lithium trifluoromethanesulfonate (0.415 g, 2.72 mmol) in acetonitrile (5 ml) are heated at 85° C. for 4.5 hours. The reaction mixture is diluted with ethyl acetate, washed with water and brine, dried (Na2SO4) and evaporated. Final purification by flash chromatography (70% Ethyl acetate/hexane) gives the title compound as a yellow solid. HPLC r.t. 3.98 min; MS for C19H26FN3O4 m/z 380.1 (M+H)+. washed with water and brine dried (Na2SO4) evaporated Final purification by flash chromatography (70% Ethyl acetate/hexane)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 5-Amino-7-fluoro-1-propyl-1,3-dihydro-indol-2-one (0.500 g, 2.40 mmol), (S)-oxiranylmethyl-carbamic acid tert-butyl ester (0.417 g, 2.40 mmol) and lithium trifluoromethanesulfonate (0.368 g, 2.40 mmol) in acetonitrile (8 ml) are heated at 90° C. for 8 hours. The reaction mixture is diluted with ethyl acetate, washed with water and brine, dried (Na2SO4) and evaporated. Final purification by flash chromatography (70% Ethyl acetate/hexane) gives the title compound as a yellow solid. HPLC r.t. 4.30 min; MS for C19H28FN3O4 m/z 382.3 (M+H)+. washed with water and brine dried (Na2SO4) evaporated Final purification by flash chromatography (70% Ethyl acetate/hexane)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 5-Amino-7-fluoro-1-(2-fluoro-ethyl)-1,3-dihydro-indol-2-one (0.39 g, 1.84 mmol), (S)-oxiranylmethyl-carbamic acid tert-butyl ester (0.319 g, 1.84 mmol) and lithium trifluoromethanesulfonate (0.283 g, 1.84 mmol) in acetonitrile (4 ml) are heated at 90° C. for 6 hours. The reaction mixture is diluted with ethyl acetate, washed with water and brine, dried (Na2SO4) and evaporated. Final purification by flash chromatography (70% Ethyl acetate/hexane) gives the title compound as a yellow-brown foamy solid. HPLC r.t. 3.92 min; MS for C18H25F2N3O4 m/z 386.1 (M+H)+. washed with water and brine dried (Na2SO4) evaporated Final purification by flash chromatography (70% Ethyl acetate/hexane)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 5-Amino-1-ethyl-7-fluoro-1,3-dihydro-indol-2-one (2.25 g, 11.6 mmol), (S)-oxiranylmethyl-carbamic acid tert-butyl ester (2.00 g, 11.6 mmol) and lithium trifluoromethanesulfonate (1.80 g, 11.6 mmol) in acetonitrile (12 ml) are heated at 90° C. for 20 hours. The reaction mixture is diluted with ethyl acetate, washed with water and brine, dried (Na2SO4) and evaporated. Final purification by flash chromatography (70% Ethyl acetate/hexane) gives the title compound as a yellow-brown foamy solid. HPLC r.t. 3.95 min; MS for C 18H26FN3O4 m/z 368.3 (M+H)+. washed with water and brine dried (Na2SO4) evaporated Final purification by flash chromatography (70% Ethyl acetate/hexane)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a slurry of [3-fluoro-4(4-morpholinyl)phenyl]carbamic acid phenylmethyl ester (Example 1) (1.0039 g, 3.039 mmol) and tert-butyl (2S)oxiranylmethylcarbamate (Example 5) (0.653 g, 3.77 mmol, 1.24 eq) in THF (1.5 ml) at 0° C. was added a solution of lithium t-butoxide in THF (18.07 wt %, 1.735 g, 3.92 mmol, 1.29 eq). After standing 2 days at 20–25° C., methylene chloride (5.0 ml), then acetic acid (0.35 ml, 6.11 mmol, 2.01 eq) followed by water (3.5 ml) was added. The phases were separated and the aqueous washed with methylene chloride (3.5 ml). The combined organics were dried on magnesium sulfate and concentrated to an oil which was shown to contain 1.03 g (85.7%) of Compound III, wherein R1=3-fluoro-4-(4-morpholinyl)phenyl, R3=t-butyl, by external standard HPLC: retention time=4.06 min (column=Zorbax SB-C8 3.5 micron 150×4.6 mm, flow rate=2.0 ml/min, gradient elution from 30:70 A:B to 90:10 A:B over 15 minutes; A=969:30:1 acetonitrile: THF: trifluoroacetic acid; B=949:50:1 water: THF:trifluroracetic acid). was added The phases were separated the aqueous washed with methylene chloride (3.5 ml) The combined organics were dried on magnesium sulfate concentrated to an oil which 3.5 micron 150×4.6 mm, flow rate=2.0 ml/min, gradient elution from 30:70 A:B to 90:10 A:B over 15 minutes