Potassium Phosphate, Tribasic → HCID 86270035, compound

HRID 2279019Notes

Reaction equation

HRID 2279019 reaction equation
Cl[C:2]1[CH:7]=[C:6]([O:8][C:9]2[C:10]([CH3:26])=[CH:11][C:12]([NH:15][C:16]([N:18]3[CH2:22][CH2:21][N:20]([CH2:23][CH3:24])[C:19]3=[O:25])=[O:17])=[N:13][CH:14]=2)[CH:5]=[CH:4][N:3]=1.[CH3:27][C:28]1[N:29]=[CH:30][NH:31][CH:32]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.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]>[CH2:23]([N:20]1[CH2:21][CH2:22][N:18]([C:16]([NH:15][C:12]2[CH:11]=[C:10]([CH3:26])[C:9]([O:8][C:6]3[CH:5]=[CH:4][N:3]=[C:2]([N:31]4[CH:32]=[C:28]([CH3:27])[N:29]=[CH:30]4)[CH:7]=3)=[CH:14][N:13]=2)=[O:17])[C:19]1=[O:25])[CH3:24]

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 90426247HCID 90426247, compoundHCID 178418800HCID 178418800, compound

Product 1

HCID 86270035HCID 86270035, compoundYield 33.3%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 1140TolueneSolvent3×HCID 312751,4-DioxaneSolvent3×

Procedure

A solution of Pd2(dba)3 (0.029 g, 0.032 mmol) and Me4t-BuXPhos (0.034 g, 0.072 mmol) in toluene (0.6 mL) and dioxane (1.2 mL) was heated at 120° C. for 3 min, cooled to RT, added to a degassed suspension of N-(5-((2-chloropyridin-4-yl)oxy)-4-methylpyridin-2-yl)-3-ethyl-2-oxoimidazolidine-1-carboxamide (0.3 g, 0.798 mmol), 4-methyl imidazole (0.085 g, 1.038 mmol) and K3PO4 (0.339 g, 1.597 mmol) in toluene (1.2 mL) and dioxane (2.4 mL) and heated at 110° C. overnight. The mixture was treated with additional catalyst (synthesized from Pd2(dba)3 (0.029 g, 0.032 mmol) and Me4t-BuXPhos (0.034 g, 0.072 mmol) in toluene (0.6 mL) and dioxane (1.2 mL) as above) and heated at 110° C. overnight. The mixture was cooled to RT, treated with satd. NaHCO3, extracted with EtOAc (5×) and the combined organics were dried over Na2SO4, concentrated to dryness and purified twice via silica gel chromatography (MeOH/DCM). The material was further purified via reverse-phase chromatography (MeCN/H2O with 0.1% TFA); the organics were removed under reduced pressure and the aqueous residue was treated with satd. NaHCO3 and extracted with DCM (3×). The combined organics were dried over Na2SO4 and concentrated to dryness to afford 3-ethyl-N-(4-methyl-5-((2-(4-methyl-1H-imidazol-1-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide (112 mg, 32%). 1H NMR (400 MHz, DMSO-d6): δ 10.93 (s, 1 H), 8.39 (d, J=1.4 Hz, 1 H), 8.30 (d, J=5.8 Hz, 1 H), 8.13 (s, 1 H), 8.02 (s, 1 H), 7.64 (s, 1 H), 7.33 (d, J=2.2 Hz, 1 H), 6.73 (dd, J=5.8, 2.2 Hz, 1 H), 3.80 (t, J=8.3 Hz, 2H), 3.46 (t, J=8.2 Hz, 2 H), 3.26-3.25 (q, J=7.2 Hz, 2 H), 2.15 (s, 3 H), 2.13 (s, 3 H), 1.09 (t, J=7.2 Hz, 3H); MS (ESI) m/z: 422.2 (M+H+).

Workup

  1. temperatureheated at 110° C. overnight
  2. temperatureheated at 110° C. overnight
  3. temperatureThe mixture was cooled to RT
  4. additiontreated with satd
  5. extractionNaHCO3, extracted with EtOAc (5×)
  6. dry with materialthe combined organics were dried over Na2SO4
  7. concentrationconcentrated to dryness
  8. custompurified twice via silica gel chromatography (MeOH/DCM)
  9. customThe material was further purified via reverse-phase chromatography (MeCN/H2O with 0.1% TFA)
  10. customthe organics were removed under reduced pressure
  11. additionthe aqueous residue was treated with satd
  12. extractionNaHCO3 and extracted with DCM (3×)
  13. dry with materialThe combined organics were dried over Na2SO4
  14. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-65d856e7cb424b9e9a06042c6b96a48a
Source dataset
uspto-grants-2015_09
Patent number
US09133183B2

Reaction notes

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