Water → N-(3-chloro-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

HRID 2279050Notes

Reaction equation

HRID 2279050 reaction equation
[Cl:1][C:2]1[C:3]([F:22])=[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:23]=[C:24]1[N:28]([CH:29]2[CH2:34][CH2:33][O:32][CH2:31][CH2:30]2)[CH2:27][CH2:26][N:25]1[C:35](Cl)=[O:36].O>C(Cl)Cl>[Cl:1][C:2]1[C:3]([F:22])=[C:4]([NH:5][C:35]([N:25]2[CH2:26][CH2:27][N:28]([CH:29]3[CH2:34][CH2:33][O:32][CH2:31][CH2:30]3)[C:24]2=[O:23])=[O:36])[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 904267863-chloro-2-fluoro-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)anilineHCID 904274552-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carbonyl chloride

Product 1

HCID 90427132N-(3-chloro-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-carboxamideYield 60%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A mixture of 3-chloro-2-fluoro-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)aniline (0.250 g, 0.784 mmol) and TEA (0.150 mL, 1.076 mmol) in DCM (5 mL) was treated drop-wise with a solution of Example B2 (0.219 g, 0.941 mmol) in DCM (5 mL), warmed to RT and stirred overnight. The mixture was treated with water, extracted with DCM (3×) and the combined organics were dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (MeOH/DCM). The material was treated with MeCN, sonicated and the resulting solid collected via filtration to afford N-(3-chloro-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 (242 mg, 60%). 1H NMR (400 MHz, DMSO-d6): δ 10.86 (s, 1 H), 8.36 (d, J=5.7 Hz, 1 H), 8.26 (s, 1 H), 8.18 (t, J=8.9 Hz, 1 H), 7.97 (s, 1 H), 7.25-7.20 (m, 2 H), 6.65 (dd, J=5.7, 2.4 Hz, 1 H), 3.90 (m, 3 H), 3.84 (s, 3 H), 3.81 (m, 2 H), 3.47 (m, 2 H), 3.38 (m, 2 H), 1.77-1.65 (m, 2 H), 1.59 (m, 2H); MS (ESI) m/z: (M+H+): 515.1.

Workup

  1. extractionextracted with DCM (3×)
  2. dry with materialthe combined organics were dried over Na2SO4
  3. concentrationconcentrated to dryness
  4. custompurified via silica gel chromatography (MeOH/DCM)
  5. additionThe material was treated with MeCN
  6. customsonicated
  7. filtrationthe resulting solid collected via filtration

Sources & evidence

ORD record
ord-22ab70203cdc4e4c8dd9cc4bdf431887
Source dataset
uspto-grants-2015_09
Patent number
US09133183B2

Reaction notes

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