Sodium Hydroxide → 3-(4-Bromo-2-fluoro-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-(4-bromo-2-fluoro-phenylamino)-thieno[3,2-c]pyridine-2-carboxylic acid ethyl ester (36 mg, 0.09 mmol), 1N aqueous NaOH solution (0.10 ml, 0.10 mmol) and methanol (2 ml) was heated at 65° C. for 45 minutes. The reaction mixture was concentrated in vacuo 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 (22 mg, 0.18 mmol), EDCI (22 mg, 0.12 mmol), HOBt (17 mg, 0.13 mmol) and DIPEA (48 μl, 0.28 mmol) were added. After stirring overnight at ambient temperature, the reaction mixture was concentrated in vacuo to afford a yellow residue. The resultant residue was dissolved in ethyl acetate (30 ml), washed with water (20 ml) followed by brine (10 ml) before the organic layer was isolated then dried over sodium sulfate and concentrated in vacuo to afford a yellow oil. The oil was purified by flash chromatography (Si-SPE, pentane:ethyl acetate, gradient 90:10 to 50:50) to afford the title compound as a yellow oil (18 mg, 41%). LCMS (method B): RT=3.03 min, M+H+=496/498.

1. concentrationThe reaction mixture was concentrated in vacuo
2. customthen azeotroped with toluene (2×2 ml)
3. customto give a solid residue
4. concentrationthe reaction mixture was concentrated in vacuo
5. customto afford a yellow residue
6. washwashed with water (20 ml)
7. customwas isolated
8. dry with materialthen dried over sodium sulfate
9. concentrationconcentrated in vacuo
10. customto afford a yellow oil
11. customThe oil was purified by flash chromatography (Si-SPE, pentane:ethyl acetate, gradient 90:10 to 50:50)

ORD record

ord-5e1defd0811d4d7a8d5ea41f136c70fa

Source dataset

uspto-grants-2011_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07893085B2