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

HRID 1012754Notes

Reaction equation

HRID 1012754 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][C:9]2=[O:14])=[CH:4][CH:3]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].[ClH:38].[N:39]12[CH2:46][CH2:45][CH:42]([CH2:43][CH2:44]1)[C@@H:41]([NH:47][C:48]([C:50]1[S:51][C:52]3[C:58](Br)=[CH:57][CH:56]=[CH:55][C:53]=3[CH:54]=1)=[O:49])[CH2:40]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:38].[N:39]12[CH2:44][CH2:43][CH:42]([CH2:45][CH2:46]1)[C@@H:41]([NH:47][C:48]([C:50]1[S:51][C:52]3[C:58]([C:2]4[CH:7]=[CH:6][C:5]([N:8]5[CH2:13][CH2:12][O:11][CH2:10][C:9]5=[O:14])=[CH:4][CH:3]=4)=[CH:57][CH:56]=[CH:55][C:53]=3[CH:54]=1)=[O:49])[CH2:40]2

Participants

8

Reactant 5

HCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 179827074-(4-Bromophenyl)morpholin-3-oneHCID 66904832N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-7-bromo-1-benzothiophene-2-carboxamide hydrochloride

Product 1

HCID 67315678N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-7-[4-(3-oxo-4-morpholinyl)phenyl]-1-benzothiophene-2-carboxamide hydrochloride

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst2×HCID 6228DimethylformamideSolvent

Procedure

120 mg (0.39 mmol) of 4-(4-bromophenyl)-3-morpholinone, 115.3 mg (0.45 mmol) of bis(pinacolato)diboron, 96.6 mg (0.98 mmol) of potassium acetate, 11.1 mg (0.02 mmol) of PdCl2(dppf), 121.6 mg (0.30 mmol) of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-7-bromo-1-benzothiophene-2-carboxamide hydrochloride (Example 8A), 0.76 ml of 2 M sodium carbonate solution and a further 11.1 mg (0.02 mmol) of PdCl2(dppf) in 2 ml of DMF are reacted by general method D. Drying under high vacuum results in 24 mg (16% of theory) of the title compound.

Workup

  1. customDrying under high vacuum

Sources & evidence

ORD record
ord-95700c1e8eb54e438ec9982318e80496
Source dataset
uspto-grants-2011_07
Patent number
US07977485B2

Reaction notes

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