Sodium Hydroxide → 3-(2-Fluoro-4-iodo-phenylamino)-thieno[3,2-c]pyridine-2-carboxylic acid ((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-amide

Temperature

65 °C

A mixture of 3-(2-fluoro-4-iodo-phenylamino)-thieno[2,3-c]pyridine-2-carboxylic acid ethyl ester (50 mg, 0.11 mmol), 1N aqueous NaOH solution (0.12 ml, 0.12 mmol) and ethanol (2 ml) was heated at 65° C. for 45 minutes. The reaction mixture was concentrated then azeotroped with toluene (2×2 ml) to give a solid residue. The solid residue was dissolved in anhydrous THF (2 ml) and O—((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)hydroxylamine (27 mg, 0.23 mmol), EDCI (27 mg, 0.14 mmol), HOBt (21 mg, 0.16 mmol) and DIPEA (59 μl, 0.34 mmol) were added. After stirring for 19 hours the solvent was evaporated and the residue partitioned between ethyl acetate (30 ml) and water (20 ml). The organic layer was dried over sodium sulphate, filtered and evaporated to give a yellow oil. The oil was purified by flash chromatography (Si-SPE, pentane:ethyl acetate, gradient 80:20 to 50:50) to afford the title compound as a yellow solid (18 mg, 30%). LCMS (method B): RT=3.09 min, M+H+=544.

1. concentrationThe reaction mixture was concentrated
2. customthen azeotroped with toluene (2×2 ml)
3. customto give a solid residue
4. customwas evaporated
5. customthe residue partitioned between ethyl acetate (30 ml) and water (20 ml)
6. dry with materialThe organic layer was dried over sodium sulphate
7. filtrationfiltered
8. customevaporated
9. customto give a yellow oil
10. customThe oil was purified by flash chromatography (Si-SPE, pentane:ethyl acetate, gradient 80:20 to 50:50)

ORD record

ord-edf6c9fc76634dfe9e08c258ecbd4ca3

Source dataset

uspto-grants-2011_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07893085B2