1-(oxan-4-yl)imidazolidin-2-one

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of Example B1 (141 mg, 0.826 mmol) and pyridine (98 mg, 1.239 mmol) in DCM (4 mL) was added to phosgene (20% in toluene, 1.021 g, 2.065 mmol), under Ar, stirred for 15 minutes, then concentrated to dryness. The residue was treated with a solution of 5-bromo-2-fluoro-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)aniline (150 mg, 0.413 mmol) and TEA (209 mg, 2.065 mmol) in DCM (4 mL) and stirred at RT for 0.5 h. The mixture was diluted with water, extracted with EtOAc (2×) and combined organics were washed with brine, dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (MeOH/EtOAc) to afford N-(5-bromo-2-fluoro-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)phenyl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide (134 mg, 58%). 1H NMR (400 MHz, DMSO-d6): δ 10.90 (d, J=2.7 Hz, 1 H), 8.54 (d, J=8.2 Hz, 1 H), 8.36 (d, J=5.7 Hz, 1 H), 8.26 (s, 1 H), 7.97 (s, 1 H), 7.55 (d, J=11.3 Hz, 1 H), 7.19 (d, J=2.4 Hz, 1 H), 6.61 (dd, J=5.7, 2.5 Hz, 1 H), 3.93-3.87 (m, 3 H), 3.84 (s, 3 H), 3.83-3.78 (m, 2 H), 3.47 (m, 2 H), 3.37 (m, 2 H), 1.71 (m, 2 H), 1.59 (m, 2H); MS (ESI) m/z: (M+H+): 559.1. concentrated to dryness stirred at RT for 0.5 h extracted with EtOAc (2×) combined organics were washed with brine dried over Na2SO4 concentrated to dryness purified via silica gel chromatography (MeOH/EtOAc)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of Example B1 (141 mg, 0.826 mmol) and pyridine (98 mg, 1.239 mmol) in DCM (4 mL) was added to phosgene (20% in toluene, 1.021 g, 2.065 mmol), under Ar, stirred for 15 minutes, then concentrated to dryness. The residue was treated with a solution of 5-bromo-2-fluoro-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)aniline (150 mg, 0.413 mmol) and TEA (209 mg, 2.065 mmol) in DCM (4 mL) and stirred at RT for 0.5 h. The mixture was diluted with water, extracted with EtOAc (2×) and combined organics were washed with brine, dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (MeOH/EtOAc) to afford N-(5-bromo-2-fluoro-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)phenyl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide (134 mg, 58%). 1H NMR (400 MHz, DMSO-d6): δ 10.90 (d, J=2.7 Hz, 1 H), 8.54 (d, J=8.2 Hz, 1 H), 8.36 (d, J=5.7 Hz, 1 H), 8.26 (s, 1 H), 7.97 (s, 1 H), 7.55 (d, J=11.3 Hz, 1 H), 7.19 (d, J=2.4 Hz, 1 H), 6.61 (dd, J=5.7, 2.5 Hz, 1 H), 3.93-3.87 (m, 3 H), 3.84 (s, 3 H), 3.83-3.78 (m, 2 H), 3.47 (m, 2 H), 3.37 (m, 2 H), 1.71 (m, 2 H), 1.59 (m, 2H); MS (ESI) m/z: (M+H+): 559.1. concentrated to dryness stirred at RT for 0.5 h extracted with EtOAc (2×) combined organics were washed with brine dried over Na2SO4 concentrated to dryness purified via silica gel chromatography (MeOH/EtOAc)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Phosgene (20% in toluene, 0.798 mL, 1.508 mmol) was treated drop-wise with a solution of Example B1 (0.128 g, 0.754 mmol) and pyridine (0.244 mL, 3.02 mmol) in DCM (5 mL), stirred at RT for 10 min, then concentrated to dryness. The residue was dissolved in DCM (5 mL), treated drop-wise with a solution of 2-fluoro-3-methyl-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)aniline (0.15 g, 0.503 mmol) and DIEA (0.527 mL, 3.02 mmol) in DCM (5 mL) stirred at RT for 3 h. The mixture was treated with satd. NaHCO3, extracted with DCM (3×) and the combined organics were dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (MeOH/DCM) to afford N-(2-fluoro-3-methyl-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)phenyl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide (0.188 g, 76%). 1H NMR (400 MHz, DMSO-d6): δ 10.76 (d, J=2.7 Hz, 1 H), 8.33 (d, J=5.7 Hz, 1 H), 8.24 (s, 1 H), 8.05 (t, J=9.0 Hz, 1 H), 7.95 (d, J=0.7 Hz, 1 H), 7.16 (d, J=2.4 Hz, 1 H), 6.98 (d, J=9.0 Hz, 1 H), 6.57 (dd, J=5.7, 2.4 Hz, 1 H), 3.93-3.83 (m, 6 H), 3.82-3.77 (m, 2 H), 3.46 (t, J=8.2 Hz, 2 H), 3.38 (dd, J=12.6, 10.8 Hz, 2 H), 2.05 (d, J=2.0 Hz, 3 H), 1.71 (m, 2 H), 1.59 (br d, J=12.3 Hz, 2H); MS (ESI) m/z: 495.2 (M+H+). concentrated to dryness The residue was dissolved in DCM (5 mL) stirred at RT for 3 h The mixture was treated with satd NaHCO3, extracted with DCM (3×) the combined organics were dried over Na2SO4 concentrated to dryness purified via silica gel chromatography (MeOH/DCM)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 0° C. solution of Example B1 (0.19 g, 1.116 mmol) and pyridine (0.26 mL, 3.21 mmol) in DCM (5 mL) was treated drop-wise with phosgene (20% in toluene, 1.4 mL, 2.65 mmol), warmed to RT over 0.5 h, then treated slowly with a solution of 6-ethyl-5-((2′-methyl-[2,4′-bipyridin]-4-yl)oxy)pyridin-2-amine (0.13 g, 0.424 mmol) and pyridine (0.16 mL, 1.978 mmol) in DCM (5 mL) and stirred at RT overnight. The mixture was treated with satd. NaHCO3, extracted with EtOAc (4×) and the combined organics were dried over MgSO4, concentrated to dryness, purified via silica gel chromatography (MeOH/DCM), then re-purified via reverse-phase chromatography (MeCN/H2O with 0.1% TFA). The organics were removed under reduced pressure, the aqueous residue treated with satd. NaHCO3, extracted with DCM (5×) and the combined organics were dried over MgSO4 and concentrated to dryness to afford N-(6-ethyl-5-((2′-methyl-[2,4′-bipyridin]-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide (8 mg, 4%). 1H NMR (400 MHz, DMSO-d6): δ 10.93 (s, 1 H), 8.56 (d, J=5.7 Hz, 1 H), 8.52 (d, J=5.3 Hz, 1 H), 7.93-7.89 (m, 2 H), 7.67 (d, J=2.4 Hz, 1 H), 7.68-7.66 (m, 1 H), 7.64 (s, 1 H), 6.86 (dd, J=5.7, 2.4 Hz, 1 H), 3.94-3.78 (m, 5 H), 3.49-3.34 (m, 4 H), 2.58 (q, J=7.5 Hz, 2 H), 2.53 (s, 3H), 1.78-1.66 (m, 2 H), 1.64-1.57 (m, 2 H), 1.12 (t, J=7.5 Hz, 3H); MS (ESI) m/z: 503.3 (M+H+). The mixture was treated with satd NaHCO3, extracted with EtOAc (4×) the combined organics were dried over MgSO4 concentrated to dryness purified via silica gel chromatography (MeOH/DCM) re-purified via reverse-phase chromatography (MeCN/H2O with 0.1% TFA) The organics were removed under reduced pressure the aqueous residue treated with satd NaHCO3, extracted with DCM (5×) the combined organics were dried over MgSO4 concentrated to dryness

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 0° C. solution of Example B1 (0.19 g, 1.116 mmol) and pyridine (0.26 mL, 3.21 mmol) in DCM (5 mL) was treated drop-wise with phosgene (20% in toluene, 1.4 mL, 2.65 mmol) and warmed to RT over 0.5 h. The mixture was treated slowly with a solution of 6-ethyl-5-((6′-methyl-[2,3′-bipyridin]-4-yl)oxy)pyridin-2-amine (0.16 g, 0.522 mmol) and pyridine (0.16 mL, 1.978 mmol) in DCM (5 mL) and stirred at RT overnight. The mixture was treated with satd. NaHCO3, extracted with EtOAc (4×) and the combined organics were dried over MgSO4, concentrated to dryness, purified via silica gel chromatography (MeOH/DCM), then re-purified via reverse-phase chromatography (MeCN/H2O with 0.1% TFA). The combined fractions were treated with satd. NaHCO3, extracted with DCM (5×) and the combined organics were dried over MgSO4 and concentrated to dryness to afford N-(6-ethyl-5-((6′-methyl-[2,3′-bipyridin]-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide (19 mg, 7%). 1H NMR (400 MHz, DMSO-d6): δ 10.93 (s, 1 H), 9.09 (d, J=2.4 Hz, 1 H), 8.52 (d, J=5.7 Hz, 1 H), 8.28 (dd, J=8.1, 2.4 Hz, 1 H), 7.90 (d, J=8.8 Hz, 1 H), 7.64 (d, J=8.8 Hz, 1 H), 7.59 (d, J=2.4 Hz, 1 H), 7.33 (d, J=8.2 Hz, 1H), 6.77 (dd, J=5.7, 2.4 Hz, 1 H), 3.94-3.84 (m, 3 H), 3.83-3.79 (m, 2 H), 3.46 (t, J=8.2 Hz, 2 H), 3.38 (t, J=11.6 Hz, 2 H), 2.58 (q, J=7.5 Hz, 2 H), 2.50 (s, 3 H), 1.72 (dd, J=12.3, 4.5 Hz, 2 H), 1.62 (s, 2 H), 1.12 (t, J=7.5 Hz, 3H); MS (ESI) m/z: 503.3 (M+H+). The mixture was treated with satd NaHCO3, extracted with EtOAc (4×) the combined organics were dried over MgSO4 concentrated to dryness purified via silica gel chromatography (MeOH/DCM) re-purified via reverse-phase chromatography (MeCN/H2O with 0.1% TFA) The combined fractions were treated with satd NaHCO3, extracted with DCM (5×) the combined organics were dried over MgSO4 concentrated to dryness

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of phosgene (15% in toluene, 1.440 g, 2.184 mmol) under Ar, was treated with a solution of Example B1 (0.149 g, 0.874 mmol) and pyridine (0.104 g, 1.310 mmol) in DCM (4 mL), stirred for 15 min, then concentrated to dryness. The residue was treated with a solution of Example A9 (0.129 g, 0.437 mmol) and TEA (0.221 g, 2.184 mmol) in DCM (4 mL), stirred for 0.5 h, then treated with water and EtOAc. The layers were separated, the aqueous layer extracted with additional EtOAc (1×) and the combined organics were washed with brine, dried over Na2SO4, concentrated to dryness and purified via reverse-phase chromatography (MeCN/H2O with 0.1% TFA). The organics were removed under reduced pressure and the aqueous residue was neutralized with satd. NaHCO3 and extracted with EtOAc (2×). The combined organics were washed with brine, dried over Na2SO4 and concentrated to dryness to afford N-(6-ethyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide (130 mg, 60%). 1H NMR (400 MHz, DMSO-d6): δ 10.91 (s, 1 H), 8.33 (d, J=5.7 Hz, 1 H), 8.24 (s, 1 H), 7.94 (d, J=0.7 Hz, 1 H), 7.89 (d, J=8.8 Hz, 1 H), 7.59 (d, J=8.8 Hz, 1 H), 7.17 (d, J=2.4 Hz, 1 H), 6.58 (dd, J=5.7, 2.4 Hz, 1 H), 3.90-3.87 (m, 3 H), 3.83 (s, 3 H), 3.81-3.79 (m, 2 H), 3.45 (t, J=8.3 Hz, 2 H), 3.37 (dd, J=12.4, 10.5 Hz, 2 H), 2.56 (q, J=7.5 Hz, 2 H), 1.71 (qd, J=12.2, 4.5 Hz, 2 H), 1.62-1.58 (m, 2 H), 1.10 (t, J=7.5 Hz, 3H); MS (ESI) m/z: 492.3 (M+H+). concentrated to dryness stirred for 0.5 h The layers were separated the aqueous layer extracted with additional EtOAc (1×) the combined organics were washed with brine dried over Na2SO4 concentrated to dryness purified via reverse-phase chromatography (MeCN/H2O with 0.1% TFA) The organics were removed under reduced pressure NaHCO3 and extracted with EtOAc (2×) The combined organics were washed with brine dried over Na2SO4 concentrated to dryness

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of phosgene (15% in toluene, 1.440 g, 2.184 mmol) under Ar, was treated with a solution of Example B1 (0.149 g, 0.874 mmol) and pyridine (0.104 g, 1.310 mmol) in DCM (4 mL), stirred for 15 min, then concentrated to dryness. The residue was treated with a solution of Example A9 (0.129 g, 0.437 mmol) and TEA (0.221 g, 2.184 mmol) in DCM (4 mL), stirred for 0.5 h, then treated with water and EtOAc. The layers were separated, the aqueous layer extracted with additional EtOAc (1×) and the combined organics were washed with brine, dried over Na2SO4, concentrated to dryness and purified via reverse-phase chromatography (MeCN/H2O with 0.1% TFA). The organics were removed under reduced pressure and the aqueous residue was neutralized with satd. NaHCO3 and extracted with EtOAc (2×). The combined organics were washed with brine, dried over Na2SO4 and concentrated to dryness to afford N-(6-ethyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide (130 mg, 60%). 1H NMR (400 MHz, DMSO-d6): δ 10.91 (s, 1 H), 8.33 (d, J=5.7 Hz, 1 H), 8.24 (s, 1 H), 7.94 (d, J=0.7 Hz, 1 H), 7.89 (d, J=8.8 Hz, 1 H), 7.59 (d, J=8.8 Hz, 1 H), 7.17 (d, J=2.4 Hz, 1 H), 6.58 (dd, J=5.7, 2.4 Hz, 1 H), 3.90-3.87 (m, 3 H), 3.83 (s, 3 H), 3.81-3.79 (m, 2 H), 3.45 (t, J=8.3 Hz, 2 H), 3.37 (dd, J=12.4, 10.5 Hz, 2 H), 2.56 (q, J=7.5 Hz, 2 H), 1.71 (qd, J=12.2, 4.5 Hz, 2 H), 1.62-1.58 (m, 2 H), 1.10 (t, J=7.5 Hz, 3H); MS (ESI) m/z: 492.3 (M+H+). concentrated to dryness stirred for 0.5 h The layers were separated the aqueous layer extracted with additional EtOAc (1×) the combined organics were washed with brine dried over Na2SO4 concentrated to dryness purified via reverse-phase chromatography (MeCN/H2O with 0.1% TFA) The organics were removed under reduced pressure NaHCO3 and extracted with EtOAc (2×) The combined organics were washed with brine dried over Na2SO4 concentrated to dryness

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Phosgene (20% in toluene, 0.613 g, 1.24 mmol) was treated with a solution of Example B1 (0.063 g, 0.37 mmol) and pyridine (0.1 mL, 1.24 mmol) in DCM (2 mL), stirred for 15 min, then concentrated to dryness. The residue was dissolved in DCM (2 mL), treated with a solution of 6-methyl-5-((2-(3-methylisoxazol-5-yl)pyridin-4-yl)oxy)pyridin-2-amine (0.07 g, 0.25 mmol) and TEA (0.17 mL, 1.24 mmol) in DCM (2 mL) and stirred at RT for 1 h. The mixture was treated with satd. NaHCO3, extracted with EtOAc (2×) and the combined organics were washed with brine, dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (MeOH/DCM) to afford N-(6-methyl-5-((2-(3-methylisoxazol-5-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide (75 mg, 63%). 1H NMR (400 MHz, DMSO-d6): δ 10.92 (s, 1 H), 8.55 (d, J=5.7 Hz, 1 H), 7.92 (d, J=8.8 Hz, 1 H), 7.67 (d, J=8.8 Hz, 1 H), 7.34 (d, J=2.5 Hz, 1 H), 6.98 (s, 1 H), 6.96 (dd, J=5.7, 2.5 Hz, 1 H), 3.95-3.77 (m, 5 H), 3.48-3.35 (m, 4 H), 2.28 (s, 3 H), 2.24 (s, 3 H), 1.71-1.70 (m, 2 H), 1.60 (d, J=12.5 Hz, 2 H); MS (ESI) m/z: 479.2 (M+H+). concentrated to dryness The residue was dissolved in DCM (2 mL) stirred at RT for 1 h The mixture was treated with satd NaHCO3, extracted with EtOAc (2×) the combined organics were washed with brine dried over Na2SO4 concentrated to dryness purified via silica gel chromatography (MeOH/DCM)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Phosgene (20% in toluene, 0.613 g, 1.24 mmol) was treated with a solution of Example B1 (0.063 g, 0.37 mmol) and pyridine (0.1 mL, 1.24 mmol) in DCM (2 mL), stirred for 15 min, then concentrated to dryness. The residue was dissolved in DCM (2 mL), treated with a solution of 6-methyl-5-((2-(3-methylisoxazol-5-yl)pyridin-4-yl)oxy)pyridin-2-amine (0.07 g, 0.25 mmol) and TEA (0.17 mL, 1.24 mmol) in DCM (2 mL) and stirred at RT for 1 h. The mixture was treated with satd. NaHCO3, extracted with EtOAc (2×) and the combined organics were washed with brine, dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (MeOH/DCM) to afford N-(6-methyl-5-((2-(3-methylisoxazol-5-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide (75 mg, 63%). 1H NMR (400 MHz, DMSO-d6): δ 10.92 (s, 1 H), 8.55 (d, J=5.7 Hz, 1 H), 7.92 (d, J=8.8 Hz, 1 H), 7.67 (d, J=8.8 Hz, 1 H), 7.34 (d, J=2.5 Hz, 1 H), 6.98 (s, 1 H), 6.96 (dd, J=5.7, 2.5 Hz, 1 H), 3.95-3.77 (m, 5 H), 3.48-3.35 (m, 4 H), 2.28 (s, 3 H), 2.24 (s, 3 H), 1.71-1.70 (m, 2 H), 1.60 (d, J=12.5 Hz, 2 H); MS (ESI) m/z: 479.2 (M+H+). concentrated to dryness The residue was dissolved in DCM (2 mL) stirred at RT for 1 h The mixture was treated with satd NaHCO3, extracted with EtOAc (2×) the combined organics were washed with brine dried over Na2SO4 concentrated to dryness purified via silica gel chromatography (MeOH/DCM)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Phosgene (20% in toluene, 0.613 g, 1.24 mmol) was treated with a solution of Example B1 (0.063 g, 0.37 mmol) and pyridine (0.1 mL, 1.24 mmol) in DCM (2 mL), stirred for 15 min, then concentrated to dryness. The residue was dissolved in DCM (2 mL), treated with a solution of 6-methyl-5-((2-(3-methylisoxazol-5-yl)pyridin-4-yl)oxy)pyridin-2-amine (0.07 g, 0.25 mmol) and TEA (0.17 mL, 1.24 mmol) in DCM (2 mL) and stirred at RT for 1 h. The mixture was treated with satd. NaHCO3, extracted with EtOAc (2×) and the combined organics were washed with brine, dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (MeOH/DCM) to afford N-(6-methyl-5-((2-(3-methylisoxazol-5-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide (75 mg, 63%). 1H NMR (400 MHz, DMSO-d6): δ 10.92 (s, 1 H), 8.55 (d, J=5.7 Hz, 1 H), 7.92 (d, J=8.8 Hz, 1 H), 7.67 (d, J=8.8 Hz, 1 H), 7.34 (d, J=2.5 Hz, 1 H), 6.98 (s, 1 H), 6.96 (dd, J=5.7, 2.5 Hz, 1 H), 3.95-3.77 (m, 5 H), 3.48-3.35 (m, 4 H), 2.28 (s, 3 H), 2.24 (s, 3 H), 1.71-1.70 (m, 2 H), 1.60 (d, J=12.5 Hz, 2 H); MS (ESI) m/z: 479.2 (M+H+). concentrated to dryness The residue was dissolved in DCM (2 mL) stirred at RT for 1 h The mixture was treated with satd NaHCO3, extracted with EtOAc (2×) the combined organics were washed with brine dried over Na2SO4 concentrated to dryness purified via silica gel chromatography (MeOH/DCM)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Phosgene (20% in toluene, 2.62 g, 5.3 mmol) was treated with a solution of Example B1 (0.27 g, 1.59 mmol) and pyridine (0.43 mL, 5.3 mmol) in DCM (5 mL), stirred for 15 min, then concentrated to dryness. The residue was dissolved in DCM (5 mL), treated with a solution of Example A7 (0.25 g, 1.06 mmol) and TEA (0.74 mL, 5.3 mmol) in DCM (5 mL) and stirred at RT for 1 h. The mixture was treated with satd. NaHCO3, extracted with EtOAc (2×) and the combined organics were washed with brine, dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (EtOAc/Hex) to afford N-(5-((2-chloropyridin-4-yl)oxy)-6-methylpyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide (0.24 g, 52%). 1H NMR (400 MHz, DMSO-d6): δ 10.91 (s, 1 H), 8.27 (d, J=5.8 Hz, 1 H), 7.90 (d, J=8.8 Hz, 1 H), 7.65 (d, J=8.8 Hz, 1 H), 7.02 (d, J=2.3 Hz, 1 H), 6.92 (dd, J=5.8, 2.3 Hz, 1 H), 3.94-3.84 (m, 5 H), 3.48-3.35 (m, 4 H), 2.21 (s, 3 H), 1.74-1.66 (m, 2 H), 1.60 (d, J=12.5 Hz, 2 H); MS (ESI) m/z: 432.1 (M+H+). concentrated to dryness The residue was dissolved in DCM (5 mL) stirred at RT for 1 h The mixture was treated with satd NaHCO3, extracted with EtOAc (2×) the combined organics were washed with brine dried over Na2SO4 concentrated to dryness purified via silica gel chromatography (EtOAc/Hex)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 0° C. solution of phosgene (20% in toluene, 0.267 mL, 0.506 mmol) in DCM (5 mL) was treated slowly drop-wise with a solution of Example B1 (0.086 g, 0.505 mmol) and pyridine (0.082 mL, 1.011 mmol) in DCM (3 mL). The mixture was warmed to RT, stirred for 1 hour, then concentrated to dryness to afford 2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carbonyl chloride as an off-white solid. The material was carried on to the next step assuming 100% yield (118 mg). MS (ESI) m/z: 304.1 (M+H+) (for material quenched into benzylamine). concentrated to dryness