Pyridine → N-(5-((2-chloropyridin-4-yl)oxy)-6-methylpyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide

HRID 2278969Notes

Reaction equation

HRID 2278969 reaction equation
[C:1](Cl)(Cl)=[O:2].[O:5]1[CH2:10][CH2:9][CH:8]([N:11]2[CH2:15][CH2:14][NH:13][C:12]2=[O:16])[CH2:7][CH2:6]1.N1C=CC=CC=1.[Cl:23][C:24]1[CH:29]=[C:28]([O:30][C:31]2[CH:32]=[CH:33][C:34]([NH2:38])=[N:35][C:36]=2[CH3:37])[CH:27]=[CH:26][N:25]=1>C(Cl)Cl>[Cl:23][C:24]1[CH:29]=[C:28]([O:30][C:31]2[CH:32]=[CH:33][C:34]([NH:38][C:1]([N:13]3[CH2:14][CH2:15][N:11]([CH:8]4[CH2:7][CH2:6][O:5][CH2:10][CH2:9]4)[C:12]3=[O:16])=[O:2])=[N:35][C:36]=2[CH3:37])[CH:27]=[CH:26][N:25]=1

Participants

6

Reactant 4

HCID 1049PyridineHCID 6371PhosgeneHCID 904029725-((2-Chloropyridin-4-yl)oxy)-6-methylpyridin-2-amineHCID 904259751-(Oxan-4-yl)imidazolidin-2-one

Product 1

HCID 90426065N-(5-((2-chloropyridin-4-yl)oxy)-6-methylpyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamideYield 52.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

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+).

Workup

  1. concentrationconcentrated to dryness
  2. dissolutionThe residue was dissolved in DCM (5 mL)
  3. stirringstirred at RT for 1 h
  4. additionThe mixture was treated with satd
  5. extractionNaHCO3, extracted with EtOAc (2×)
  6. washthe combined organics were washed with brine
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated to dryness
  9. custompurified via silica gel chromatography (EtOAc/Hex)

Sources & evidence

ORD record
ord-231a34df98fa43c48509a972f93b54f0
Source dataset
uspto-grants-2015_09
Patent number
US09133183B2

Reaction notes

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