Cesium carbonate → HCID 86270409, compound

HRID 2279035Notes

Reaction equation

HRID 2279035 reaction equation
[Cl:1][C:2]1[C:3]([O:24][C:25]2[CH:30]=[CH:29][N:28]=[C:27](Cl)[CH:26]=2)=[CH:4][C:5]([F:23])=[C:6]([NH:8][C:9]([N:11]2[CH2:15][CH2:14][N:13]([CH:16]3[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)[C:12]2=[O:22])=[O:10])[CH:7]=1.[CH3:32][N:33]([CH3:37])[C:34]([NH2:36])=[O:35].C([O-])([O-])=O.[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:1][C:2]1[C:3]([O:24][C:25]2[CH:30]=[CH:29][N:28]=[C:27]([NH:36][C:34]([N:33]([CH3:37])[CH3:32])=[O:35])[CH:26]=2)=[CH:4][C:5]([F:23])=[C:6]([NH:8][C:9]([N:11]2[CH2:15][CH2:14][N:13]([CH:16]3[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)[C:12]2=[O:22])=[O:10])[CH:7]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 11737N,N-DimethylureaHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 90426423HCID 90426423, compound

Product 1

HCID 86270409HCID 86270409, compoundYield 44.2%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of Example C8 (0.200 g, 0.426 mmol), N,N-dimethyl urea (0.225 g, 2.56 mmol), Cs2CO3 (0.347 g, 1.065 mmol) and Xantphos (0.074 g, 0.128 mmol) in dioxane (3 mL) was sparged with Ar, treated Pd2(dba)3 (0.051 g, 0.055 mmol), sparged again with Ar and heated at 100° C. overnight. The mixture was cooled to RT, treated with brine, extracted with EtOAc (3×) and the combined organics were dried over Na2SO4, concentrated to dryness and purified twice via silica gel chromatography (MeOH/DCM, then MeOH/EtOAc). The material was suspended in 1:1 EtOAc/Et2O, sonicated and the resulting solid collected via filtration to afford N-(5-chloro-4-((2-(3,3-dimethylureido)pyridin-4-yl)oxy)-2-fluorophenyl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide (98 mg, 44%). 1H NMR (400 MHz, DMSO-d6): δ 10.92 (d, J=2.7 Hz, 1 H), 8.91 (s, 1 H), 8.39 (d, J=8.0 Hz, 1 H), 8.10 (d, J=5.7 Hz, 1 H), 7.56 (d, J=11.2 Hz, 1 H), 7.34 (d, J=2.4 Hz, 1 H), 6.56 (dd, J=5.7, 2.4 Hz, 1 H), 3.93-3.86 (m, 3 H), 3.83-3.81 (m, 2 H), 3.47 (m, 2H), 3.37 (m, 2 H), 2.87 (s, 6 H), 1.71 (m, 2 H), 1.59 (m, 2H); MS (ESI) m/z: 521.2 (M+H+).

Workup

  1. customsparged again with Ar
  2. temperatureThe mixture was cooled to RT
  3. additiontreated with brine
  4. extractionextracted with EtOAc (3×)
  5. dry with materialthe combined organics were dried over Na2SO4
  6. concentrationconcentrated to dryness
  7. custompurified twice via silica gel chromatography (MeOH/DCM
  8. customsonicated
  9. filtrationthe resulting solid collected via filtration

Sources & evidence

ORD record
ord-d61145b66f3d471b98cff6415b0d9d28
Source dataset
uspto-grants-2015_09
Patent number
US09133183B2

Reaction notes

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