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

HRID 1012763Notes

Reaction equation

HRID 1012763 reaction equation
Br[C:2]1[CH:3]=[C:4]([N:8]2[CH:12]=[CH:11][CH:10]=[CH:9]2)[CH:5]=[CH:6][CH:7]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].[ClH:36].[N:37]12[CH2:44][CH2:43][CH:40]([CH2:41][CH2:42]1)[C@@H:39]([NH:45][C:46]([C:48]1[S:49][C:50]3[C:56](Br)=[CH:55][CH:54]=[CH:53][C:51]=3[CH:52]=1)=[O:47])[CH2:38]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:36].[N:37]12[CH2:42][CH2:41][CH:40]([CH2:43][CH2:44]1)[C@@H:39]([NH:45][C:46]([C:48]1[S:49][C:50]3[C:56]([C:2]4[CH:7]=[CH:6][CH:5]=[C:4]([N:8]5[CH:12]=[CH:11][CH:10]=[CH:9]5)[CH:3]=4)=[CH:55][CH:54]=[CH:53][C:51]=3[CH:52]=1)=[O:47])[CH2:38]2

Participants

8

Reactant 5

HCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 6428181-(3-bromophenyl)-1H-pyrroleHCID 2733548Bis(pinacolato)diboraneHCID 66904832N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-7-bromo-1-benzothiophene-2-carboxamide hydrochloride

Product 1

HCID 67313745N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-7-[3-(1H-pyrrol-1-yl)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

124.4 mg (0.56 mmol) of 1-(3-bromophenyl)-1H-pyrrole, 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 2.0 ml of DMF are reacted by general method D. Drying under high vacuum results in 86.9 mg (48% of theory) of the title compound.

Workup

  1. customDrying under high vacuum

Sources & evidence

ORD record
ord-e24483622d1b41ff86f9dfcb8c2d5b46
Source dataset
uspto-grants-2011_07
Patent number
US07977485B2

Reaction notes

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