2-Methyltetrahydrofuran → HCID 57386416, Verbindung

HRID 539370

Reaktionsgleichung

Reaktionsgleichung von HRID 539370
CC([PH+](C(C)(C)C)CCCS([O-])(=O)=O)(C)C.[Cl:17][C:18]1[CH:19]=[C:20](B(O)O)[CH:21]=[N:22][CH:23]=1.Br[C:28]1[CH:37]=[C:36]2[C:31]([CH2:32][CH2:33][CH2:34][C:35]32[N:41]=[C:40]([NH2:42])[C:39]([CH3:43])=[N:38]3)=[CH:30][CH:29]=1.CC1CCCO1.C([O-])([O-])=O.[K+].[K+]>[Na+].[Na+].Cl[Pd+2](Cl)(Cl)Cl>[Cl:17][C:18]1[CH:19]=[C:20]([C:28]2[CH:37]=[C:36]3[C:31]([CH2:32][CH2:33][CH2:34][C:35]43[N:41]=[C:40]([NH2:42])[C:39]([CH3:43])=[N:38]4)=[CH:30][CH:29]=2)[CH:21]=[N:22][CH:23]=1

Komponenten

7

Edukt 5

HCID 73012-MethyltetrahydrofuranHCID 11430Potassium CarbonateHCID 201118775-Chloropyridine-3-boronic acidHCID 249491873-(Di-tert-butylphosphonium)propane sulfonateHCID 57386415HCID 57386415, Verbindung

Produkt 1

HCID 57386416HCID 57386416, VerbindungAusbeute 33,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 178479786HCID 178479786, VerbindungKatalysator

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

Sodium tetrachloropalladate(II) (3.52 mg, 0.01 mmol), 3-(di-tert-butylphosphonium)propane sulfonate (6.43 mg, 0.02 mmol), 5-chloropyridin-3-ylboronic acid (51.6 mg, 0.31 mmol) and 7′-bromo-5-methyl-3′,4′-dihydro-2′H-spiro[imidazole-2,1′-naphthalen]-4-amine (Example 51 Step 4, 70 mg, 0.24 mmol) were added to a vial. 2-Methyl-tetrahydrofuran (1 mL) and K2CO3 (2M aq.) (0.359 mL, 0.72 mmol) were added and the mixture was degassed by bubbling N2 (g). The vial was sealed and heated in a microwave reactor at 90° C. for 30 min. EtOAc (5 mL) and water (5 mL) were added and the phases were separated. The aqueous phase was extracted with EtOAc twice and the combined organic layers were dried over MgSO4, filtered and concentrated in vacuo. The crude product was purified by flash chromatography (4 g SiO2, 0-10% MeOH containing 0.1M NH3 in DCM). The fractions containing product were combined and concentrated, yielding the title compound (26 mg, 33% yield). 1H NMR (500 MHz, CD3OD) δ ppm 1.85-1.94 (m, 1 H), 2.01 (ddd, 1 H), 2.08-2.17 (m, 1 H), 2.17-2.27 (m, 1 H), 2.35 (s, 3 H), 3.02 (t, 2 H), 6.84 (d, 1 H), 7.34 (d, 1 H), 7.48 (dd, 1 H), 7.97 (t, 1 H), 8.48 (d, 1 H), 8.57 (d, 1 H); MS (ES+) m/z 325 [M+H]+.

Aufarbeitung

  1. customthe mixture was degassed
  2. customby bubbling N2 (g)
  3. customThe vial was sealed
  4. additionEtOAc (5 mL) and water (5 mL) were added
  5. customthe phases were separated
  6. extractionThe aqueous phase was extracted with EtOAc twice
  7. dry with materialthe combined organic layers were dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude product was purified by flash chromatography (4 g SiO2, 0-10% MeOH containing 0.1M NH3 in DCM)
  11. additionThe fractions containing product
  12. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-f21ad1a3f0a04e6e93b1d496692b7c07
Quelldatensatz
uspto-grants-2014_10
Patentnummer
US08865911B2

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