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

Participants

Role	Name	HCID	Charge
Reactant	Sodium Carbonate	HCID 10340	—
Reactant	2-Thiopheneboronic acid	HCID 2733960	—
Reactant	N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-7-bromo-1-benzothiophene-2-carboxamide hydrochloride	HCID 66904832	—
Catalyst	Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)	HCID 178418228	—
Solvent	Dimethylformamide	HCID 6228	—
Product	N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-7-(2-thienyl)-1-benzothiophene-2-carboxamide formate	HCID 67313664	—

Reaction Conditions

Temperature	85 °C

Reaction Steps

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.

Provenance & Evidence

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