Sodium Iodide → 3-(2-Fluoro-4-iodo-phenylamino)-thieno[2,3-c]pyridine-2-carboxylic acid ethyl ester

Temperature

105 °C

A mixture of 3-(4-bromo-2-fluoro-phenylamino)-thieno[3,2-c]pyridine-2-carboxylic acid ethyl ester (209 mg, 0.53 mmol), copper (1) iodide (5 mg, 0.026 mmol), sodium iodide (159 mg, 1.06 mmol) and trans-N,N′-dimethyl-1,2-cyclohexane diamine (8.5 g, 0.053 mmol) in 1,4-dioxane (1.0 ml) was heated at 105° C. for 24 hours under an argon atmosphere. Copper (1) iodide (5 mg, 0.026 mmol) and trans-N,N′-dimethyl-1,2-cyclohexane diamine (8.5 μl, 0.053 mmol) were added and heating continued for a further 24 h. Once the reaction was cooled to room temperature, the mixture was partitioned between ethyl acetate (30 ml) and 10% v/v 0.880 ammonia/water (20 ml). The layers were separated and the aqueous phase was extracted with DCM (30 ml). The combined organic layer was dried over sodium sulphate, filtered and evaporated then the residue was purified by flash chromatography a Si-SPE (eluting with pentane:diethyl ether, gradient 90:10 to 70:30) to afford the title compound as a yellow solid (174 mg, 74%). LCMS (method B): RT=3.97 min, M+H+=443.

1. temperatureheating
2. temperatureOnce the reaction was cooled to room temperature
3. customthe mixture was partitioned between ethyl acetate (30 ml) and 10% v/v 0.880 ammonia/water (20 ml)
4. customThe layers were separated
5. extractionthe aqueous phase was extracted with DCM (30 ml)
6. dry with materialThe combined organic layer was dried over sodium sulphate
7. filtrationfiltered
8. customevaporated
9. customthe residue was purified by flash chromatography a Si-SPE (eluting with pentane:diethyl ether, gradient 90:10 to 70:30)

ORD record

ord-6cebf7837a864393a668b50a9c27a9f8

Source dataset

uspto-grants-2011_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07893085B2