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

温度

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 (4 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 (20 ml) and water (15 ml). The organic layer was isolated, dried over sodium sulphate, filtered and evaporated to give a brown oil. The oil was purified by flash chromatography (Si-SPE, pentane:ethyl acetate, gradient 80:20 to 0:100) to afford the title compound as an orange oil (40 mg, 66%). LCMS (method B): RT=3.30 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 (20 ml) and water (15 ml)
6. customThe organic layer was isolated
7. dry with materialdried over sodium sulphate
8. filtrationfiltered
9. customevaporated
10. customto give a brown oil
11. customThe oil was purified by flash chromatography (Si-SPE, pentane:ethyl acetate, gradient 80:20 to 0:100)

ORDレコード

ord-1714bdf776c34173808da1bf981c487a

出典データセット

uspto-grants-2011_02

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07893085B2