Sodium Carbonate → N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-7-[4-(hydroxymethyl)phenyl]-1-benzothiophene-2-carboxamide hydrochloride

HRID 2179610Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2179610
[ClH:1].[N:2]12[CH2:9][CH2:8][CH:5]([CH2:6][CH2:7]1)[C@@H:4]([NH:10][C:11]([C:13]1[S:14][C:15]3[C:21](Br)=[CH:20][CH:19]=[CH:18][C:16]=3[CH:17]=1)=[O:12])[CH2:3]2.[OH:23][CH2:24][C:25]1[CH:30]=[CH:29][C:28](B(O)O)=[CH:27][CH:26]=1.C(=O)([O-])[O-].[Na+].[Na+]>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].CN(C=O)C>[ClH:1].[N:2]12[CH2:9][CH2:8][CH:5]([CH2:6][CH2:7]1)[C@@H:4]([NH:10][C:11]([C:13]1[S:14][C:15]3[C:21]([C:28]4[CH:29]=[CH:30][C:25]([CH2:24][OH:23])=[CH:26][CH:27]=4)=[CH:20][CH:19]=[CH:18][C:16]=3[CH:17]=1)=[O:12])[CH2:3]2

Komponenten

6

Edukt 3

HCID 10340Sodium CarbonateHCID 27347064-(Hydroxymethyl)benzeneboronic acidHCID 66904832N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-7-bromo-1-benzothiophene-2-carboxamide hydrochloride

Produkt 1

HCID 67313350N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-7-[4-(hydroxymethyl)phenyl]-1-benzothiophene-2-carboxamide hydrochloride

Reagenzien, Katalysatoren, Lösungsmittel 2

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

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

60 mg (0.15 mmol) of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-7-bromo-1-benzothiophene-2-carboxamide hydrochloride (Example 8A) and 22.7 mg (0.15 mmol) of 4-(hydroxymethyl)phenylboronic acid are introduced into 1 ml of DMF. Addition of 0.22 ml of 2 M aqueous sodium carbonate solution and 6.1 mg (0.01 mmol) of PdCl2(dppf) is followed by heating to 80° C. After 14 h, the reaction mixture is filtered through kieselguhr and evaporated to dryness. The crude product is purified by preparative HPLC. The product is dissolved in methanol and an excess of 4N hydrogen chloride in dioxane is added. Drying under high vacuum results in 9 mg (9% of theory) of the title compound.

Aufarbeitung

  1. filtrationthe reaction mixture is filtered through kieselguhr
  2. customevaporated to dryness
  3. customThe crude product is purified by preparative HPLC
  4. dissolutionThe product is dissolved in methanol
  5. additionan excess of 4N hydrogen chloride in dioxane is added
  6. customDrying under high vacuum

Quellen und Nachweise

ORD-Eintrag
ord-57109484bb0d4d4f84710ac6548fc349
Quelldatensatz
uspto-grants-2015_06
Patentnummer
US09067931B2

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