Sodium Hydroxide → N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-5-[4-(4-morpholinyl)phenyl]-1-benzofuran-2-carboxamide hydrochloride

HRID 2179650Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2179650
[N:1]1([C:7]2[CH:12]=[CH:11][C:10](B(O)O)=[CH:9][CH:8]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[OH-].[Na+].[ClH:18].[N:19]12[CH2:26][CH2:25][CH:22]([CH2:23][CH2:24]1)[C@@H:21]([NH:27][C:28]([C:30]1[O:31][C:32]3[CH:38]=[CH:37][C:36](Br)=[CH:35][C:33]=3[CH:34]=1)=[O:29])[CH2:20]2>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[ClH:18].[N:19]12[CH2:24][CH2:23][CH:22]([CH2:25][CH2:26]1)[C@@H:21]([NH:27][C:28]([C:30]1[O:31][C:32]3[CH:38]=[CH:37][C:36]([C:10]4[CH:11]=[CH:12][C:7]([N:1]5[CH2:6][CH2:5][O:4][CH2:3][CH2:2]5)=[CH:8][CH:9]=4)=[CH:35][C:33]=3[CH:34]=1)=[O:29])[CH2:20]2

Komponenten

6

Edukt 3

HCID 14798Sodium HydroxideHCID 2795359(4-(Morpholin-4-yl)phenyl)boronic acidHCID 67314004N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-5-bromo-1-benzofuran-2-carboxamide hydrochloride

Produkt 1

HCID 67314243N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-5-[4-(4-morpholinyl)phenyl]-1-benzofuran-2-carboxamide hydrochloride

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

177 mg (0.86 mmol) of 4-(4-morpholinyl)phenylboronic acid and 2.15 ml of 1N sodium hydroxide solution are added to a mixture of 250 mg (0.72 mmol) of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-5-bromo-1-benzofuran-2-carboxamide (Example 3A) and 52 mg (0.07 mmol) of PdCl2(dppf) in 3 ml of DMF. The reaction mixture is heated at 90° C. overnight. The solvent is removed under reduced pressure, and the crude product is taken up in methanol and filtered through kieselguhr. Purification takes place by preparative HPLC. The product fractions are concentrated and dissolved in acetonitrile/water, and an excess of 1N hydrochloric acid is added. The solvent is removed under reduced pressure. Drying under high vacuum results in 23 mg (7% of theory) of the title compound.

Aufarbeitung

  1. customThe solvent is removed under reduced pressure
  2. filtrationfiltered through kieselguhr
  3. customPurification
  4. concentrationThe product fractions are concentrated
  5. dissolutiondissolved in acetonitrile/water
  6. additionan excess of 1N hydrochloric acid is added
  7. customThe solvent is removed under reduced pressure
  8. customDrying under high vacuum

Quellen und Nachweise

ORD-Eintrag
ord-51493b92b9064b8c95f81b65f6b44509
Quelldatensatz
uspto-grants-2015_06
Patentnummer
US09067931B2

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