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

HRID 1012758Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1012758
FC(F)(F)S(O[C:7]1[CH:12]=[CH:11][C:10]([C:13]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)=[O:14])=[CH:9][CH:8]=1)(=O)=O.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].[ClH:46].[N:47]12[CH2:54][CH2:53][CH:50]([CH2:51][CH2:52]1)[C@@H:49]([NH:55][C:56]([C:58]1[S:59][C:60]3[C:66](Br)=[CH:65][CH:64]=[CH:63][C:61]=3[CH:62]=1)=[O:57])[CH2:48]2.C(=O)([O-])[O-].[Na+].[Na+]>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:46].[N:47]12[CH2:52][CH2:51][CH:50]([CH2:53][CH2:54]1)[C@@H:49]([NH:55][C:56]([C:58]1[S:59][C:60]3[C:66]([C:7]4[CH:8]=[CH:9][C:10]([C:13]([N:15]5[CH2:16][CH2:17][O:18][CH2:19][CH2:20]5)=[O:14])=[CH:11][CH:12]=4)=[CH:65][CH:64]=[CH:63][C:61]=3[CH:62]=1)=[O:57])[CH2:48]2

Komponenten

8

Edukt 5

HCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 179828654-(4-Morpholinylcarbonyl)phenyl trifluoromethanesulphonateHCID 66904832N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-7-bromo-1-benzothiophene-2-carboxamide hydrochloride

Produkt 1

HCID 67314168N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-7-[4-(4-morpholinylcarbonyl)phenyl]-1-benzothiophene-2-carboxamide hydrochloride

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Katalysator2×HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

164.7 mg (0.49 mmol) of 4-(4-morpholinylcarbonyl)phenyl trifluoromethane-sulphonate (Example 18A), 142.2 mg (0.56 mmol) of bis(pinacolato)diboron, 119.1 mg (1.21 mmol) of potassium acetate, 13.7 mg (0.02 mmol) of PdCl2(dppf), 150.0 mg (0.37 mmol) of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-7-bromo-1-benzothiophene-2-carboxamide hydrochloride (Example 8A), 0.93 ml of 2 M sodium carbonate solution and a further 13.7 mg (0.02 mmol) of PdCl2(dppf) in 2.5 ml of DMF are reacted by general method D. An initial purification by preparative HPLC is followed by column chromatography on silica gel (mobile phase: dichloromethane/methanol/ammonia 90:9:1). Drying under high vacuum results in 24.8 mg (13% of theory) of the title compound.

Aufarbeitung

  1. customAn initial purification by preparative HPLC
  2. customDrying under high vacuum

Quellen und Nachweise

ORD-Eintrag
ord-ae8d2fcd9cc140bda25cf167ea411e63
Quelldatensatz
uspto-grants-2011_07
Patentnummer
US07977485B2

Notizen zur Reaktion

Wird geladen…