ethyl N-methylsulfonylcarbamate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mixture of compound 10b (82 mg, 0.18 mmol) and compound 12a (0.14 g, 0.86 mmol) in DMF (2 mL) was added DIEA (0.16 mL, 0.91 mmol). The mixture was stirred at 100° C. for 2 h. The solution was cooled down, and diluted with DCM (10 mL). The organic layer was washed with 1 N HCl solution (10 mL) and brine, dried over MgSO4, filtered and concentrated. The resulting residue was purified by flash column chromatography on silica gel (0-10% CH3OH/DCM) to give the title compound 50 as a red solid. 1H-NMR (400 MHz, DMSO-d6) δ (ppm): 8.96 (s, 1H), 8.31 (d, J=8.6 Hz, 1H), 8.12 (d, J=5.6 Hz, 1H), 7.94 (dd, J=13.6, 8.2 Hz, 2H), 7.83 (d, J=8.6 Hz, 1H), 7.66-7.77 (m, 5H), 7.57-7.63 (m, 2H), 7.51-7.57 (m, 1H), 6.40 (d, J=5.9 Hz, 1H), 4.03-4.14 (m, 4H), 3.83-3.92 (m, 4H), 3.17 (s, 3H). Mass Spectrum (LCMS, ESI pos.) Calcd. For C29H27N7O4S: 570.2 (M+H). Found 570.4. The solution was cooled down The organic layer was washed with 1 N HCl solution (10 mL) and brine dried over MgSO4 filtered concentrated The resulting residue was purified by flash column chromatography on silica gel (0-10% CH3OH/DCM)

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

実験手順: To a mixture of methanesulfonamide (1.0 g, 11 mmol), triethylamine (1.9 mL, 14 mmol), and DMAP (0.13 g, 1.1 mmol) in DCM (20 mL) cooled in an ice-water bath was added ethyl carbonochloridate (1.1 mL, 12 mmol) dropwise via a syringe under an argon atmosphere. The mixture was allowed to warm up to rt overnight. The reaction mixture was concentrated, and the residue obtained was dissolved in EtOAc (100 mL). The solution was washed with 1 N HCl (20 mL) and brine, and dried over MgSO4. The mixture was filtered and concentrated to give compound 12a as a yellow oil. 1H-NMR (400 MHz, CDCl3) δ (ppm): 7.86 (br. s., 1H), 4.28 (q, J=7.25 Hz, 2H), 3.30 (s, 3H), 1.33 (t, J=7.25 Hz, 3H). cooled in an ice-water bath The reaction mixture was concentrated the residue obtained The solution was washed with 1 N HCl (20 mL) and brine dried over MgSO4 The mixture was filtered concentrated

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

実験手順: To a mixture of methanesulfonamide (1.0 g, 11 mmol), triethylamine (1.9 mL, 14 mmol), and DMAP (0.13 g, 1.1 mmol) in DCM (20 mL) cooled in an ice-water bath was added ethyl carbonochloridate (1.1 mL, 12 mmol) dropwise via a syringe under an argon atmosphere. The mixture was allowed to warm up to rt overnight. The reaction mixture was concentrated, and the residue obtained was dissolved in EtOAc (100 mL). The solution was washed with 1 N HCl (20 mL) and brine, and dried over MgSO4. The mixture was filtered and concentrated to give compound 12a as a yellow oil. 1H-NMR (400 MHz, CDCl3) δ (ppm): 7.86 (br. s., 1H), 4.28 (q, J=7.25 Hz, 2H), 3.30 (s, 3H), 1.33 (t, J=7.25 Hz, 3H). cooled in an ice-water bath The reaction mixture was concentrated the residue obtained The solution was washed with 1 N HCl (20 mL) and brine dried over MgSO4 The mixture was filtered concentrated

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: N-[2-[(3S)-3-Amino-1-pyrrolidinyl]-6-chloro-5-quinolinyl]-cyclohexaneacetamide (Example 31) (0.15 g) and (methylsulfonyl)-carbamic acid ethyl ester (0.065 g) were heated with a single mode microwave in a sealed 10 mL vial for 30 minutes at 130° C. The residue was purified on a Varian® NH2 cartridge washed with methanol (50 mL) and eluted with acetic acid:methanol (10:90) to afford the title product (0.016 g). The residue was purified on a Varian® NH2 cartridge washed with methanol (50 mL) eluted with acetic acid:methanol (10:90)

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

実験手順: N-[2-[(3S)-3-Amino-1-pyrrolidinyl]-6-chloro-5-quinolinyl]-cyclohexaneacetamide (Example 31) (0.15 g) and (methylsulfonyl)-carbamic acid ethyl ester (0.065 g) were heated with a single mode microwave in a sealed 10 mL vial for 30 minutes at 130° C. The residue was purified on a Varian® NH2 cartridge washed with methanol (50 mL) and eluted with acetic acid:methanol (10:90) to afford the title product (0.016 g). The residue was purified on a Varian® NH2 cartridge washed with methanol (50 mL) eluted with acetic acid:methanol (10:90)

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of compound 59a (100 mg, 0.147 mmol) and ethyl methylsulfonylcarbamate (148 mg, 0.888 mmol) and DIEA (0.191 mL, 1.11 mmol) in DMF (2 mL) was stirred at 100° C. for 2 h. The reaction mixture was allowed to cool to rt and diluted with DCM. The reaction mixture was concentrated and the residue obtained was purified by flash column chromatography on silica gel (0-20% MeOH/EtOAc), recrystallized with EtOAc/heptanes and purified by prep-TLC (1:5:5 MeOH/DCM/EtOAc) to give the title compound 40. 1H-NMR (400 MHz, CDCl3) δ (ppm): 3.22-3.30 (m, 2H), 3.33 (s, 3H), 3.37-3.47 (m, 2H), 3.69-3.87 (m, 4H), 4.03-4.21 (m, 4H), 7.16 (s, 1H), 7.31 (s, 1H), 7.28 (s, 1H), 7.39 (d, J=8.3 Hz, 1H), 7.43-7.60 (m, 3H), 7.67-7.76 (m, 1H), 7.82 (d, J=7.6 Hz, 1H), 8.05 (d, J=8.3 Hz, 1H), 8.15 (d, J=8.3 Hz, 1H), 8.81 (br. s., 1H). Mass Spectrum LCMS, ESI (pos.) Calcd. for C29H29N7O4S: 572.2 [M+H]. found 572.5. to cool to rt The reaction mixture was concentrated the residue obtained was purified by flash column chromatography on silica gel (0-20% MeOH/EtOAc) recrystallized with EtOAc/heptanes purified by prep-TLC (1:5:5 MeOH/DCM/EtOAc)

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mixture of compound 10b (82 mg, 0.18 mmol) and compound 12a (0.14 g, 0.86 mmol) in DMF (2 mL) was added DIEA (0.16 mL, 0.91 mmol). The mixture was stirred at 100° C. for 2 h. The solution was cooled down, and diluted with DCM (10 mL). The organic layer was washed with 1 N HCl solution (10 mL) and brine, dried over MgSO4, filtered and concentrated. The resulting residue was purified by flash column chromatography on silica gel (0-10% CH3OH/DCM) to give the title compound 50 as a red solid. 1H-NMR (400 MHz, DMSO-d6) δ (ppm): 8.96 (s, 1H), 8.31 (d, J=8.6 Hz, 1H), 8.12 (d, J=5.6 Hz, 1H), 7.94 (dd, J=13.6, 8.2 Hz, 2H), 7.83 (d, J=8.6 Hz, 1H), 7.66-7.77 (m, 5H), 7.57-7.63 (m, 2H), 7.51-7.57 (m, 1H), 6.40 (d, J=5.9 Hz, 1H), 4.03-4.14 (m, 4H), 3.83-3.92 (m, 4H), 3.17 (s, 3H). Mass Spectrum (LCMS, ESI pos.) Calcd. For C29H27N7O4S: 570.2 (M+H). Found 570.4. The solution was cooled down The organic layer was washed with 1 N HCl solution (10 mL) and brine dried over MgSO4 filtered concentrated The resulting residue was purified by flash column chromatography on silica gel (0-10% CH3OH/DCM)

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

実験手順: To a mixture of methanesulfonamide (1.0 g, 11 mmol), triethylamine (1.9 mL, 14 mmol), and DMAP (0.13 g, 1.1 mmol) in DCM (20 mL) cooled in an ice-water bath was added ethyl carbonochloridate (1.1 mL, 12 mmol) dropwise via a syringe under an argon atmosphere. The mixture was allowed to warm up to rt overnight. The reaction mixture was concentrated, and the residue obtained was dissolved in EtOAc (100 mL). The solution was washed with 1 N HCl (20 mL) and brine, and dried over MgSO4. The mixture was filtered and concentrated to give compound 12a as a yellow oil. 1H-NMR (400 MHz, CDCl3) δ (ppm): 7.86 (br. s., 1H), 4.28 (q, J=7.25 Hz, 2H), 3.30 (s, 3H), 1.33 (t, J=7.25 Hz, 3H). cooled in an ice-water bath The reaction mixture was concentrated the residue obtained The solution was washed with 1 N HCl (20 mL) and brine dried over MgSO4 The mixture was filtered concentrated