Accela 1250 uhplc

Example 246

First eluting diastereomer: ¹H NMR (400 MHz, Acetonitrile-d3) δ 7.90 (s, 1H), 7.40-7.31 (m, 2H), 7.26-7.12 (m, 3H), 6.83-6.65 (m, 2H), 6.34 (s, 2H), 5.90 (d, J=6.0 Hz, 1H), 5.83 (dd, J=6.0, 4.5 Hz, 1H). 5.69 (d, J=4.5 Hz, 1H), 4.67 (dq, J=8.5, 4.2 Hz, 1H), 4.49 (dd, J=11.2, 6.1 Hz, 1H), 4.40 (dd, J=11.2, 5.4 Hz, 1H), 4.31-4.23 (m, 1H), 3.84 (ddd, J=10.0, 9.0, 7.1 Hz, 1H), 2.65 (dp, J=26.9, 7.0 Hz, 2H), 2.58-2.39 (m, 2H), 2.25-2.14 (m, 5H), 1.79 (d, J=6.8 Hz, 2H), 1.61 (dtd, J=12.6, 8.6, 3.8 Hz, 2H), 1.22 (m, 9H), 1.19 (d, J=7.0 Hz, 3H), 1.15 (d, J=7.0 Hz, 3H). ³¹P NMR (162 MHz, Acetonitrile-d3) 2.41. LCMS: m/z=756.17, t_R=1.13 min; LC system: Thermo Accela 1250 UHPLC; MS system: Thermo LCQ Fleet; Column: Phenomenex Kinetex 2.6μ XB-C18 100A, 50×3.0 mm; Solvents: acetonitrile with 0.1% formic acid, water with 0.1% formic acid; Gradient: 0 min-1.8 min 2-100% acetonitrile, 1.8 min-1.85 min 100%-2% acetonitrile, 1.85 min-2.00 min 2% ACN at 1800 μL/min. HPLC: t_R=4.68 min; HPLC system: Agilent 1290 II; Column: Phenomenex Kinetex C18, 2.6u 110A, 100×4.6 mm; Solvents: A: Water with 0.1% TFA, B: Acetonitrile with 0.1% TFA; Gradient: 2-98% B with 8.5 min gradient at 1.5 mL/min.

Example 226

First Eluting Diastereomer: ¹H NMR (400 MHz, Methanol-d₄) δ 7.80 (s, 1H), 7.34-7.25 (m, 2H), 7.24-7.11 (m, 3H), 6.85 (d, J=4.6 Hz, 1H), 6.77 (d, J=4.5 Hz, 1H), 5.96 (d, J=5.9 Hz, 1H), 5.84 (dd, J=5.9, 4.4 Hz, 1H), 5.68 (d, J=4.5 Hz, 1H), 4.51 (dd, J=11.0, 5.7 Hz, 1H), 4.41 (dd, J=11.1, 4.9 Hz, 1H), 4.05 (td, J=6.6, 5.6 Hz, 1H), 3.94-3.74 (m, 1H), 2.64 (dp, J=14.0, 7.0 Hz, 2H), 1.64-1.50 (m, 3H), 1.43-1.13 (m, 16H), 0.89 (t, J=7.4 Hz, 4H). ³¹P NMR (162 MHz, Methanol-d₄) δ 3.07. LCMS: MS m/z=715.14 [M+1], t_R=1.21 min; LC system: Thermo Accela 1250 UHPLC; MS system: Thermo LCQ Fleet; Column: Kinetex 2.6μ XB-C18 100A, 50×3.0 mm; Solvents: acetonitrile with 0.1% formic acid, water with 0.1% formic acid; Gradient: 0 min-1.8 min 2-100% acetonitrile, 1.8 min-1.85 min 100%-2% acetonitrile, 1.85 min-2.00 min 2% ACN at 1800 μL/min. HPLC: t_R=6.183 min; HPLC system: Agilent 1100 series; Column: Gemini 5μ C18 110A, 50×4.6 mm; Solvents: Acetonitrile with 0.1% TFA, Water with 0.1% TFA; Gradient: 0 min-9.0 min 2-95% ACN, 9.0 min-10.0 min 95% ACN at 2 mL/min.

Example 258

Second eluting diastereomer: ¹H NMR (400 MHz, Acetonitrile-d₃) δ 7.90 (s, 1H), 7.34 (dd, J=8.6, 7.1 Hz, 2H), 7.23-7.13 (m, 3H), 6.80-6.73 (m, 2H), 6.34 (s, 2H), 5.86 (d, J=6.0 Hz, 1H), 5.81 (dd, J=5.9, 4.5 Hz, 1H), 5.67 (d, J=4.5 Hz, 1H), 4.52-4.31 (m, 3H), 4.03-3.87 (m, 2H), 3.82 (d, J=10.8 Hz, 1H), 2.64 (m, 2H), 1.30 (dd, J=7.2, 1.0 Hz, 3H), 1.26-1.09 (m, 21H). ³¹P NMR (162 MHz, Acetonitrile-d3) δ 2.52. LCMS m/z=731.14 (M+H), t_R=1.36 min; LC system: Thermo Accela 1250 UHPLC; MS system: Thermo LCQ Fleet; Column: Phenomenex Kinetex 2.6μ XB-C18 100A, 50×3.0 mm; Solvents: acetonitrile with 0.1% formic acid, water with 0.1% formic acid; Gradient: 0 min-1.8 min 2-100% acetonitrile, 1.8 min-1.85 min 100%-2% acetonitrile, 1.85 min-2.00 min 2% ACN at 1800 μL/min. HPLC: t_R=5.36 min; HPLC system: Agilent 1290 II; Column: Phenomenex Kinetex C18, 2.6u 110A, 100×4.6 mm; Solvents: A: Water with 0.1% TFA, B: Acetonitrile with 0.1% TFA; Gradient: 2-8% B with 8.5 min gradient at 1.5 mL/min.

Example 189

Second Eluting Diastereomer: ¹H NMR (400 MHz, Methanol-d₄) δ 7.83 (s, 1H), 7.36-7.26 (m, 2H), 7.24-7.12 (m, 3H), 6.84 (d, J=4.5 Hz, 1H), 6.75 (d, J=4.6 Hz, 1H), 5.91 (d, J=5.9 Hz, 1H), 5.82 (dd, J=5.9, 4.7 Hz, 1H), 5.69 (d, J=4.7 Hz, 1H), 4.51-4.37 (m, 2H), 4.06-3.83 (m, 3H), 2.54-2.35 (m, 4H), 1.59 (dtd, J=14.0, 7.4, 6.6 Hz, 2H), 1.29 (dd, J=7.1, 1.1 Hz, 3H), 1.15 (dt, J=14.0, 7.6 Hz, 6H), 0.89 (t, J=7.4 Hz, 3H). ³¹P NMR (162 MHz, Methanol-d₄) δ 3.05. LCMS: MS m/z=673.34 [M+1], t_R=1.04 min; LC system: Thermo Accela 1250 UHPLC; MS system: Thermo LCQ Fleet; Column: Kinetex 2.6μ XB-C18 100A, 50×3.0 mm; Solvents: acetonitrile with 0.1% formic acid, water with 0.1% formic acid; Gradient: 0 min-1.8 min 2-100% acetonitrile, 1.8 min-1.85 min 100%-2% acetonitrile, 1.85 min-2.00 min 2% ACN at 1800 μL/min. HPLC: t_R=4.87 min; HPLC system: Agilent 1100 series; Column: Gemini 5μ C18 110A, 50×4.6 mm; Solvents: Acetonitrile with 0.1% TFA, Water with 0.1% TFA; Gradient: 0 min-9.0 min 2-95% ACN, 9.0 min-10.0 min 95% ACN at 2 mL/min.

Example 93

Second Eluting Diastereomer: ¹H NMR (400 MHz, methanol-d₄) δ 7.83 (s, 1H), 7.30 (t, J=7.8 Hz, 2H), 7.23-7.12 (m, 3H), 6.84 (d, J=4.5 Hz, 1H), 6.74 (d, J=4.5 Hz, 1H), 5.90 (d, J=6.0 Hz, 1H), 5.80 (dd, J=5.9, 4.7 Hz, 1H), 5.68 (d, J=4.7 Hz, 1H), 4.43 (dd, J=5.8, 4.3 Hz, 2H), 4.01 (dd, J=10.9, 6.8 Hz, 1H), 3.96-3.85 (m, 2H), 2.62-2.43 (m, 2H), 2.47-2.34 (m, 3H), 1.99 (ddd, J=10.6, 8.2, 4.8 Hz, 2H), 1.96-1.77 (m, 2H), 1.80-1.66 (m, 2H), 1.28 (dd, J=7.1, 1.1 Hz, 3H), 1.15 (dt, J=13.8, 7.5 Hz, 6H). ³¹P NMR (162 MHz, methanol-d₄) δ 3.01 LCMS: MS m/z=699.29 [M+1], t_R=1.13 min; LC system: Thermo Accela 1250 UHPLC; MS system: Thermo LCQ Fleet; Column: Phenomenex Kinetex 2.6μ XB-C18 100A, 50×3.0 mm; Solvents: acetonitrile with 0.1% formic acid, water with 0.1% formic acid; Gradient: 0 min-1.8 min 2-100% acetonitrile, 1.8 min-1.85 min 100%-2% acetonitrile, 1.85 min-2.00 min 2% ACN at 1800 μL/min. HPLC: t_R=5.793 min; Agilent 1290 II; Column: Phenomenex Kinetex C18, 2.6u 110A, 100×4.6 mm; Solvents: A: Water with 0.1% TFA, B: Acetonitrile with 0.1% TFA; Gradient: 2-98% B with 8.5 min gradient at 1.5 mL/min.

Example 178

First eluting diastereomer: ¹H NMR (400 MHz, Acetonitrile-d3) δ 7.89 (s, 1H), 7.35 (d, J=8.5 Hz, 2H), 7.23-7.11 (m, 2H), 6.77 (t, J=3.4 Hz, 2H), 6.40 (s, 2H), 5.89 (d, J=6.0 Hz, 1H), 5.83 (dd, J=5.9, 4.4 Hz, 1H), 5.69 (d, J=4.3 Hz, 1H), 4.91 (p, J=6.3 Hz, 1H), 4.50 (dd, J=11.2, 6.1 Hz, 1H), 4.43 (dd, J=11.2, 5.6 Hz, 1H), 4.36 (dd, J=12.3, 10.0 Hz, 1H), 3.80 (ddt, J=16.5, 9.5, 7.1 Hz, 1H), 3.01 (s, 3H), 2.91 (s, 3H), 2.66 (m, 2H), 1.35-1.08 (m, 21H). ³¹P NMR (162 MHz, Acetonitrile-d3) δ 2.31. LCMS: MS m/z=772.48 [M+1]; t_R=1.03 min; LC system: Thermo Accela 1250 UHPLC; MS system: Thermo LCQ Fleet; Column: Phenomenex Kinetex 2.6μ XB-C18 100A, 50×3.0 mm; Solvents: acetonitrile with 0.1% formic acid, water with 0.1% formic acid; Gradient: 0 min-1.8 min 2-100% acetonitrile, 1.8 min-1.85 min 100%-2% acetonitrile, 1.85 min-2.00 min 2% ACN at 1800 μL/min. HPLC: t_R=5.39 min; HPLC system: Agilent 1290 II; Column: Phenomenex Kinetex C18, 2.6u 110A, 100×4.6 mm; Solvents: A: Water with 0.1% TFA, B: Acetonitrile with 0.1% TFA; Gradient: 2-98% B with 8.5 min gradient at 1.5 mL/min

Example 165

Second eluting diastereomer: ¹H NMR (400 MHz, Acetonitrile-d3) δ 7.91 (s, 1H), 7.35 (t, J=7.8 Hz, 2H), 7.21 (ddd, J=8.3, 2.6, 1.4 Hz, 3H), 6.77 (q, J=4.6 Hz, 2H), 6.35 (s, 2H), 5.83-5.74 (m, 2H), 5.68 (d, J=4.6 Hz, 1H), 4.84 (tt, J=8.2, 4.0 Hz, 1H), 4.46 (dd, J=11.2, 6.7 Hz, 1H), 4.42-4.26 (m, 2H), 4.00-3.83 (m, 1H), 3.78 (dt, J=10.6, 4.8 Hz, 2H), 3.51-3.39 (m, 2H), 2.15 (s, 3H), 2.07 (s, 3H), 1.80 (q, J=10.4, 7.4 Hz, 2H), 1.53 (dtd, J=12.7, 8.4, 3.9 Hz, 2H), 1.28 (dd, J=7.1, 1.0 Hz, 3H). ³¹P NMR (162 MHz, Acetonitrile-d3) δ 2.49. LCMS: MS m/z=687.37 [M+1]; t_R=0.86 min; LC system: Thermo Accela 1250 UHPLC; MS system: Thermo LCQ Fleet; Column: Phenomenex Kinetex 2.6μ XB-C18 100A, 50×3.0 mm; Solvents: acetonitrile with 0.1% formic acid, water with 0.1% formic acid; Gradient: 0 min-1.8 min 2-100% acetonitrile, 1.8 min-1.85 min 100%-2% acetonitrile, 1.85 min-2.00 min 2% ACN at 1800 μL/min. HPLC: t_R=4.69 min; HPLC system: Agilent 1290 II; Column: Phenomenex Kinetex C18, 2.6u 110A, 100×4.6 mm; Solvents: A: Water with 0.1% TFA, B: Acetonitrile with 0.1% TFA; Gradient: 2-98% B with 8.5 min gradient at 1.5 mL/min.