Cesium carbonate → HCID 131733477, compound

HRID 2279051Notes

Reaction equation

HRID 2279051 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.[C:32](=[O:39])([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])[NH2:33].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[CH:7]=[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])[C:5]([F:23])=[CH:4][C:3]=1[O:24][C:25]1[CH:30]=[CH:29][N:28]=[C:27]([NH:33][C:32](=[O:39])[O:34][C:35]([CH3:38])([CH3:37])[CH3:36])[CH:26]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 77922tert-Butyl carbamateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 90426423HCID 90426423, compound

Product 1

HCID 131733477HCID 131733477, compoundYield 113%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

A mixture of Example C8 (1 g, 2.131 mmol), t-butyl carbamate (0.749 g, 6.39 mmol), Cs2CO3 (2.083 g, 6.39 mmol) and Xantphos (0.555 g, 0.959 mmol) in dioxane (15 mL) was sparged with Ar, treated with Pd2(dba)3 (0.293 g, 0.320 mmol), sparged again with Ar and heated at 100° C. overnight. The mixture was cooled to RT, treated with satd. NaHCO3, extracted with EtOAc (3×) and the combined organics were dried over Na2SO4, passed through a pad of silica gel and concentrated to dryness to afford crude tert-butyl (4-(2-chloro-5-fluoro-4-(2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamido)phenoxy)pyridin-2-yl)carbamate (1.32 g, 113%) which was used without further purification. MS (ESI) m/z: (M+H+): 550.1.

Workup

  1. customsparged again with Ar
  2. temperatureThe mixture was cooled to RT
  3. additiontreated with satd
  4. extractionNaHCO3, extracted with EtOAc (3×)
  5. dry with materialthe combined organics were dried over Na2SO4
  6. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-7d612de34b7745b0ab3199e858b0faca
Source dataset
uspto-grants-2015_09
Patent number
US09133183B2

Reaction notes

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