Ethyl Acetate → 3-(2-methoxyethyl)-N-(6-methyl-5-((2-(1-methyl-1H-imidazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide

HRID 2279015Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2279015
Cl[C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:10]=[CH:11][C:12]([NH:16][C:17]([N:19]3[CH2:23][CH2:22][N:21]([CH2:24][CH2:25][O:26][CH3:27])[C:20]3=[O:28])=[O:18])=[N:13][C:14]=2[CH3:15])[CH:5]=[CH:4][N:3]=1.[CH3:29][N:30]1[CH:34]=[C:33]([Sn](CCCC)(CCCC)CCCC)[N:32]=[CH:31]1.[F-].[K+].CCOC(C)=O>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:27][O:26][CH2:25][CH2:24][N:21]1[CH2:22][CH2:23][N:19]([C:17]([NH:16][C:12]2[CH:11]=[CH:10][C:9]([O:8][C:6]3[CH:5]=[CH:4][N:3]=[C:2]([C:33]4[N:32]=[CH:31][N:30]([CH3:29])[CH:34]=4)[CH:7]=3)=[C:14]([CH3:15])[N:13]=2)=[O:18])[C:20]1=[O:28]

Komponenten

7

Edukt 4

HCID 8857Ethyl AcetateHCID 522689Potassium FluorideHCID 219011411-Methyl-4-(tributylstannyl)-1H-imidazoleHCID 90426033N-(5-((2-chloropyridin-4-yl)oxy)-6-methylpyridin-2-yl)-3-(2-methoxyethyl)-2-oxoimidazolidine-1-carboxamide

Produkt 1

HCID 862696483-(2-methoxyethyl)-N-(6-methyl-5-((2-(1-methyl-1H-imidazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamideAusbeute 36,5 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
105 °C

Versuchsvorschrift

A mixture of Example C5 (0.150 g, 0.370 mmol), N-methyl-4-(tributylstannyl)imidazole (0.178 g, 0.480 mmol) and Pd(PPh3)4 (0.021 g, 0.018 mmol) in toluene (4 mL) was sparged with Ar and heated at 105° C. overnight. The mixture was cooled to RT, treated with 10% KF and EtOAc, stirred for 2 h and the solids removed via filtration through diatomaceous earth. The filtrate was extracted with EtOAc (3×) and the combined organics were washed with 10% KF, then brine, dried over Na2SO4 and concentrated to dryness. The material was treated with MeCN, sonicated, the solid removed via filtration and the filtrate concentrated to dryness and purified via silica gel chromatography (MeOH/DCM). The material was suspended in MeCN, sonicated and the solid collected via filtration. The filtrate was concentrated to dryness and further purified via reverse-phase chromatography (MeCN/H2O with 0.1% TFA). The organics were removed under reduced pressure, the aqueous residue treated with satd. NaHCO3, extracted with EtOAc (3×) and the combined organics were dried over Na2SO4, concentrated to dryness and combined with the above-isolated solid to afford 3-(2-methoxyethyl)-N-(6-methyl-5-((2-(1-methyl-1H-imidazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide (61 mg, 36%). 1H NMR (400 MHz, DMSO-d6): δ 10.89 (s, 1 H), 8.35 (d, J=5.7 Hz, 1 H), 7.91 (d, J=8.8 Hz, 1H), 7.67 (d, J=1.3 Hz, 1 H), 7.64 (d, J=8.8 Hz, 1 H), 7.59 (d, J=1.3 Hz, 1 H), 7.16 (d, J=2.6 Hz, 1 H), 6.74 (dd, J=5.7, 2.6 Hz, 1 H), 3.84-3.78 (m, 2 H), 3.67 (s, 3 H), 3.54-3.47 (m, 4 H), 3.41-3.37 (m, 2 H), 3.26 (s, 3 H), 2.23 (s, 3H); MS (ESI) m/z: 452.2 (M+H+).

Aufarbeitung

  1. temperatureThe mixture was cooled to RT
  2. customthe solids removed via filtration through diatomaceous earth
  3. extractionThe filtrate was extracted with EtOAc (3×)
  4. washthe combined organics were washed with 10% KF
  5. dry with materialbrine, dried over Na2SO4
  6. concentrationconcentrated to dryness
  7. additionThe material was treated with MeCN
  8. customsonicated
  9. customthe solid removed via filtration
  10. concentrationthe filtrate concentrated to dryness
  11. custompurified via silica gel chromatography (MeOH/DCM)
  12. customsonicated
  13. filtrationthe solid collected via filtration
  14. concentrationThe filtrate was concentrated to dryness
  15. customfurther purified via reverse-phase chromatography (MeCN/H2O with 0.1% TFA)
  16. customThe organics were removed under reduced pressure
  17. additionthe aqueous residue treated with satd
  18. extractionNaHCO3, extracted with EtOAc (3×)
  19. dry with materialthe combined organics were dried over Na2SO4
  20. concentrationconcentrated to dryness

Quellen und Nachweise

ORD-Eintrag
ord-2a70cd92b777435f912e2ab728c5156e
Quelldatensatz
uspto-grants-2015_09
Patentnummer
US09133183B2

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