Pyridine → HCID 90426325, compound

HRID 2279043Notes

Reaction equation

HRID 2279043 reaction equation
[O:1]1[CH2:6][CH2:5][CH:4]([N:7]2[CH2:11][CH2:10][NH:9][C:8]2=[O:12])[CH2:3][CH2:2]1.N1C=CC=CC=1.[C:19](Cl)(Cl)=[O:20].[Br:23][C:24]1[C:25]([O:32][C:33]2[CH:38]=[CH:37][N:36]=[C:35]([C:39]3[CH:40]=[N:41][N:42]([CH3:44])[CH:43]=3)[CH:34]=2)=[CH:26][C:27]([F:31])=[C:28]([CH:30]=1)[NH2:29]>C(Cl)Cl.O>[Br:23][C:24]1[C:25]([O:32][C:33]2[CH:38]=[CH:37][N:36]=[C:35]([C:39]3[CH:40]=[N:41][N:42]([CH3:44])[CH:43]=3)[CH:34]=2)=[CH:26][C:27]([F:31])=[C:28]([NH:29][C:19]([N:9]2[CH2:10][CH2:11][N:7]([CH:4]3[CH2:3][CH2:2][O:1][CH2:6][CH2:5]3)[C:8]2=[O:12])=[O:20])[CH:30]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 6371PhosgeneHCID 904259751-(Oxan-4-yl)imidazolidin-2-oneHCID 90426054HCID 90426054, compound

Product 1

HCID 90426325HCID 90426325, compoundYield 58%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

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.

Workup

  1. concentrationconcentrated to dryness
  2. stirringstirred at RT for 0.5 h
  3. extractionextracted with EtOAc (2×)
  4. washcombined organics were washed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated to dryness
  7. custompurified via silica gel chromatography (MeOH/EtOAc)

Sources & evidence

ORD record
ord-75e30c1013824359b3e81386baa4cf74
Source dataset
uspto-grants-2015_09
Patent number
US09133183B2

Reaction notes

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