Cesium carbonate → 1-(3-Methyl-4-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)-3-(3-(trifluoromethyl)phenyl)imidazolidin-2-one

HRID 446343Notes

Reaction equation

HRID 446343 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([N:23]2[CH2:27][CH2:26][NH:25][C:24]2=[O:28])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[C:14]([C:15]2[CH:20]=[CH:19][N:18]=[C:17]([NH:21][CH3:22])[N:16]=2)=[CH:13][CH:12]=[CH:11][N:10]=1.I[C:30]1[CH:35]=[CH:34][CH:33]=[C:32]([C:36]([F:39])([F:38])[F:37])[CH:31]=1.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.ClCCl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:1][C:2]1[CH:3]=[C:4]([N:23]2[CH2:27][CH2:26][N:25]([C:30]3[CH:35]=[CH:34][CH:33]=[C:32]([C:36]([F:39])([F:38])[F:37])[CH:31]=3)[C:24]2=[O:28])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[C:14]([C:15]2[CH:20]=[CH:19][N:18]=[C:17]([NH:21][CH3:22])[N:16]=2)=[CH:13][CH:12]=[CH:11][N:10]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 67868Benzene, 1-iodo-3-(trifluoromethyl)-HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 669705671-(3-Methyl-4-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)imidazolidin-2-one

Product 1

HCID 585883301-(3-Methyl-4-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)-3-(3-(trifluoromethyl)phenyl)imidazolidin-2-one

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

1-(3-methyl-4-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)imidazolidin-2-one (0.100 g, 0.266 mmol), 1-iodo-3-(trifluoromethyl)benzene (0.050 mL, 0.35 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (0.012 g, 0.020 mmol), palladium (II) acetate (0.009 g, 0.013 mmol), and cesium carbonate (0.130 g, 0.399 mmol) were combined in dioxane under argon. The reaction vessel was sealed and the mixture was heated to 100 deg. C. for 48 h. The reaction was cooled to ambient temperature and diluted with dichloromethane, filtered, and concentrated in vacuo. The resulting material was adsorbed onto silica gel and purified by silica gel chromatography. The resulting material was further purified by reverse-phase HPLC using acetonitrile/water/TFA eluent to give 1-(3-methyl-4-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)-3-(3-(trifluoromethyl)phenyl)imidazolidin-2-one as a white solid. MS m/z=521 [M+1]+. Calc'd for C27H23F3N6O2: 520.51.

Workup

  1. customThe reaction vessel was sealed
  2. temperaturethe mixture was heated to 100 deg. C
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. custompurified by silica gel chromatography
  6. customThe resulting material was further purified by reverse-phase

Sources & evidence

ORD record
ord-05214a1a18be422fadb58079a280ef3a
Source dataset
uspto-grants-2013_07
Patent number
US08476434B2

Reaction notes

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