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

온도

65 °C

A mixture of ethyl 3-(4-bromo-2-fluoro-phenylamino)-thieno[2,3-c]pyridine-2-carboxylate (63 mg, 0.16 mmol), 1N aqueous NaOH solution (0.17 ml, 0.17 mmol) and ethanol (2 ml) was heated at 65° C. for 45 minutes. The resultant reaction mixture was concentrated in vacuo then the residue was azeotroped with toluene (2×2 ml) to give a solid residue. The resultant solid residue was suspended in anhydrous THF (2 ml) before O—((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)hydroxylamine (38 mg, 0.32 mmol), EDCI (38 mg, 0.20 mmol), HOBt (30 mg, 0.22 mmol) and DIPEA (83 μl. 0.48 mmol) were added. After stirring for 66 hours at ambient temperature, the reaction mixture was concentrated in vacuo to afford a yellow residue. The resultant residue was dissolved in ethyl acetate (50 ml) and washed with water (20 ml), before the organic layer was isolated, dried over sodium sulfate, then concentrated in vacuo to afford a yellow oil. The oil was purified by flash chromatography (Si-SPE, pentane:ethyl acetate, gradient 60:40 to 0:100) to afford the title compound as a yellow foam (61 mg, 77%). LCMS (method B): RT=3.02 min, M+H+=496/498.

1. customThe resultant reaction mixture
2. concentrationwas concentrated in vacuo
3. customthe residue was azeotroped with toluene (2×2 ml)
4. customto give a solid residue
5. additionwere added
6. concentrationthe reaction mixture was concentrated in vacuo
7. customto afford a yellow residue
8. washwashed with water (20 ml), before the organic layer
9. customwas isolated
10. dry with materialdried over sodium sulfate
11. concentrationconcentrated in vacuo
12. customto afford a yellow oil
13. customThe oil was purified by flash chromatography (Si-SPE, pentane:ethyl acetate, gradient 60:40 to 0:100)

ORD 기록

ord-39c0261fd4fe462ba2a9c634036db539

출처 데이터셋

uspto-grants-2011_02

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US07893085B2