Water → N-(3-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

HRID 2279038Notes

Reaction equation

HRID 2279038 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[O:9][C:10]1[CH:15]=[CH:14][N:13]=[C:12]([C:16]2[CH:17]=[N:18][N:19]([CH3:21])[CH:20]=2)[CH:11]=1)[NH2:5].[O:22]=[C:23]1[N:27]([CH:28]2[CH2:33][CH2:32][O:31][CH2:30][CH2:29]2)[CH2:26][CH2:25][N:24]1[C:34](Cl)=[O:35].O>C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]([NH:5][C:34]([N:24]2[CH2:25][CH2:26][N:27]([CH:28]3[CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)[C:23]2=[O:22])=[O:35])[CH:6]=[CH:7][C:8]=1[O:9][C:10]1[CH:15]=[CH:14][N:13]=[C:12]([C:16]2[CH:17]=[N:18][N:19]([CH3:21])[CH:20]=2)[CH:11]=1

Participants

5

Reactant 3

HCID 962WaterHCID 593227693-fluoro-4-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)anilineHCID 904274552-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carbonyl chloride

Product 1

HCID 90426642N-(3-fluoro-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)phenyl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamideYield 61%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A 0° C. mixture of 3-fluoro-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)aniline (0.150 g, 0.528 mmol) and TEA (0.1 mL, 0.716 mmol) in DCM (5 mL) was treated with a solution of Example B2 (0.164 g, 0.705 mmol) in DCM (1.5 mL), warmed to RT and stirred for 1 h. The mixture was treated with water, stirred for 10 min, the layers separated and the organic layer dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (MeOH/DCM). The material was treated with DCM, sonicated and allowed to evaporate overnight. The residue was treated with Et2O, sonicated and the resulting solid collected via filtration to afford N-(3-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 (154 mg, 61%). 1H NMR (400 MHz, DMSO-d6): δ 10.59 (s, 1 H), 8.35 (d, J=5.7 Hz, 1 H), 8.25 (s, 1 H), 7.95 (s, 1 H), 7.74 (dd, J=12.9, 2.2 Hz, 1 H), 7.36-7.28 (m, 2 H), 7.22 (d, J=2.5 Hz, 1 H), 6.62 (dd, J=5.7, 2.5 Hz, 1 H), 3.94-3.82 (m, 6 H), 3.79 (m, 2 H), 3.45 (m, 2 H), 3.37 (m, 2 H), 1.72 (m, 2 H), 1.59 (m, 2H); MS (ESI) m/z: (M+H+): 481.2.

Workup

  1. stirringstirred for 10 min
  2. customthe layers separated
  3. dry with materialthe organic layer dried over Na2SO4
  4. concentrationconcentrated to dryness
  5. custompurified via silica gel chromatography (MeOH/DCM)
  6. additionThe material was treated with DCM
  7. customsonicated
  8. customto evaporate overnight
  9. additionThe residue was treated with Et2O
  10. customsonicated
  11. filtrationthe resulting solid collected via filtration

Sources & evidence

ORD record
ord-394f97351bc4418f8e43c0c352537493
Source dataset
uspto-grants-2015_09
Patent number
US09133183B2

Reaction notes

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