Sodium Carbonate → Tert-butyl 4-(4-aminothieno[3,2-c]pyridin-3-yl)phenylcarbamate

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Reaction Steps

A suspension of 3-bromothieno[3,2-c]pyridin-4-amine (13.7 g, 59.7 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylcarbamate (20 g, 62.7 mmol), tetrakis(triphenylphosphine)palladium(0) (2.5 g, 2.1 mmol) and Na2CO3 (13.3 g, 125 mmol) in tetrahydrofuran (150 mL), methanol (40 mL) and water (80 mL) was degassed, then stirred at reflux overnight. The reaction mixture was cooled to room temperature, then partitioned between ethyl acetate and water. The aqueous layer was extracted with additional ethyl acetate and the combined organics were dried (using MgSO4), filtered and the filtrate was concentrated. The residue was purified via silica gel chromatography eluting with 50 to 70% ethyl acetate-hexanes to give crude tert-butyl 4-(4-aminothieno[3,2-c]pyridin-3-yl)phenylcarbamate. A solution of the crude product (59.7 mmol based on 100% yield) in N,N-dimethylformamide (80 mL) was treated with N-iodosuccinimide (13.5 g, 59.7 mol-added in portions) and the resulting dark solution was stirred at room temperature for 2 hours, then partitioned between water (500 mL) and ethyl acetate (100 mL) with NaCl added to facilitate layer separation. The aqueous layer was extracted with additional ethyl acetate (2×75 mL) and the combined organics were washed with sodium thiosulfate (3×20 mL) and brine (50 mL), and then dried (using MgSO4), filtered, and concentrated. The crude material was treated with TFA (20 mL) and CH2Cl2 (5 mL), stirred at room temperature for 2 hours, concentrated under a stream of nitrogen, then concentrated in vacuo. The solid was dissolved in water (100 mL), carefully treated with solid Na2CO3 until gas evolution ceased and filtered, washing with additional water. The solid collected was dried to provide the title compound as a solid (contaminated by ca. 10% mole PPh3).

Provenance & Evidence