Potassium Carbonate → N-(6-methyl-5-((2'-methyl-[2,4'-bipyridin]-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide

HRID 2279018Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2279018
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]([CH:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)[C:20]3=[O:30])=[O:18])=[N:13][C:14]=2[CH3:15])[CH:5]=[CH:4][N:3]=1.C([O-])([O-])=O.[K+].[K+].[CH3:37][C:38]1[CH:43]=[C:42](B2OC(C)(C)C(C)(C)O2)[CH:41]=[CH:40][N:39]=1>O1CCOCC1.O.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>[CH3:15][C:14]1[N:13]=[C:12]([NH:16][C:17]([N:19]2[CH2:23][CH2:22][N:21]([CH:24]3[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)[C:20]2=[O:30])=[O:18])[CH:11]=[CH:10][C:9]=1[O:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([C:42]2[CH:41]=[CH:40][N:39]=[C:38]([CH3:37])[CH:43]=2)[CH:7]=1

Komponenten

7

Edukt 3

HCID 11430Potassium CarbonateHCID 164142742-Methylpyridine-4-boronic acid pinacol esterHCID 90426065N-(5-((2-chloropyridin-4-yl)oxy)-6-methylpyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide

Produkt 1

HCID 86269851N-(6-methyl-5-((2'-methyl-[2,4'-bipyridin]-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamideAusbeute 35,4 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A mixture of Example C3 (0.377 g, 0.873 mmol) and K2CO3 (0.362 g, 2.62 mmol) in dioxane (4 mL) and water (1 mL) was sparged with Ar, treated with 2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.201 g, 0.917 mmol) and Pd(Ph3P)4 (0.101 g, 0.087 mmol), sparged again with Ar and heated at 80° C. overnight. The mixture was cooled to RT, diluted with EtOAc, dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (MeOH/EtOAc). The material was treated with Et2O, stirred at RT and the resulting solid collected via filtration and dried to afford N-(6-methyl-5-((2′-methyl-[2,4′-bipyridin]-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide (151 mg, 35%). 1H NMR (400 MHz, DMSO-d6): δ 10.90 (s, 1 H), 8.56 (d, J=5.6 Hz, 1 H), 8.52 (d, J=5.2 Hz, 1 H), 7.93-7.88 (m, 2 H), 7.79 (dd, J=5.3, 1.6 Hz, 1 H), 7.66-7.63 (m, 2 H), 6.86 (dd, J=5.6, 2.4 Hz, 1 H), 3.93-3.77 (m, 5 H), 3.49-3.34 (m, 4 H), 2.52 (s, 3 H), 2.26 (s, 3 H), 1.78-1.66 (m, 2 H), 1.63-1.57 (m, 2H); MS (ESI) m/z: 489.2 (M+H+).

Aufarbeitung

  1. customsparged again with Ar
  2. temperatureThe mixture was cooled to RT
  3. additiondiluted with EtOAc
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated to dryness
  6. custompurified via silica gel chromatography (MeOH/EtOAc)
  7. additionThe material was treated with Et2O
  8. filtrationthe resulting solid collected via filtration
  9. customdried

Quellen und Nachweise

ORD-Eintrag
ord-ba4561cecccc43629a1d83a8110aa757
Quelldatensatz
uspto-grants-2015_09
Patentnummer
US09133183B2

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