Sodium Carbonate → N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-7-(2-thienyl)-1-benzothiophene-2-carboxamide formate

HRID 1012745Notes

Reaction equation

Cl.[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.[S:23]1[CH:27]=[CH:26][CH:25]=[C:24]1B(O)O.[C:31](=O)([O-:33])[O-:32].[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>[CH:31]([OH:33])=[O:32].[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:24]4[S:23][CH:27]=[CH:26][CH:25]=4)=[CH:20][CH:19]=[CH:18][C:16]=3[CH:17]=1)=[O:12])[CH2:3]2

Participants

Conditions

Temperature: 85 °C

Procedure

100 mg (0.25 mmol) of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-7-bromo-1-benzothiophene-2-carboxamide hydrochloride (Example 8A) and 31.9 mg (0.25 mmol) of 2-thiopheneboronic acid are introduced into 1.5 ml of DMF. Addition of 0.37 ml of 2 M sodium carbonate solution and 9.11 mg (0.01 mmol) of PdCl2(dppf) is followed by heating to 85° C. After 14 h, the reaction mixture is filtered through kieselguhr and purified by preparative HPLC (eluent A: acetonitrile, eluent B: water+0.1% formic acid; gradient: 10% A→95% A). The product fractions are concentrated and dried under high vacuum. 30 mg (28% of theory) of the title compound are obtained.

Workup

filtrationthe reaction mixture is filtered through kieselguhr
custompurified by preparative HPLC (eluent A: acetonitrile, eluent B: water+0.1% formic acid; gradient: 10% A→95% A)
concentrationThe product fractions are concentrated
customdried under high vacuum

Sources & evidence

ORD record: ord-d2e4778b9a7844ebb850cbb970384dde
Source dataset: uspto-grants-2011_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07977485B2

Reaction notes

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