Sodium hydride → HCID 53577548, compound

Temperature

0 °C

To a (0° C.) cooled and stirred solution of 5-bromothiophene-2-carboxylic acid (1.91 g, 9.25 mmol) in DCM (20 mL) was added oxalyl chloride (4.05 mL, 46.2 mmol) followed by the addition of catalytic amount of DMF. Reaction was allowed to stir at 0° C. for 2 h. The resulting reaction mixture was then concentrated under vacuum, obtained residue was dissolved in DMF (2 mL) and added to a separately prepared (0° C.) cooled mixture containing 3-methylpyridin-4-amine (1.23 g, 11.37 mmol) and sodium hydride (0.444 g, 18.49 mmol) in DMF (10 mL). After stirring the reaction at RT overnight, quenched with ice cold water (20 mL), followed by the addition of ethyl acetate (30 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (3×20 mL). The combined organic layers were washed with water (2×50 mL), brine (20 mL), dried (Na2SO4) and filtered. The filtrate was concentrated under vacuum and the crude product was purified by flash column chromatography (silica gel, DCM-methanol system as eluent) to afford 1.10 g (40%) of the title product as a white solid. 1HNMR (400 MHz, CDCl3) δ 8.44 (d, J=5.5 Hz, 1H), 8.40 (s, 1H), 8.14 (d, J=5.5 Hz, 1H), 7.70 (s, 1H), 7.40 (d, J=4.0 Hz, 1H), 7.13 (d, J=4.0 Hz, 1H), ESI-MS (m/z) 297, 298 [(MH)+ Br79,81].

1. customReaction
2. customThe resulting reaction mixture
3. concentrationwas then concentrated under vacuum
4. customobtained residue
5. additionadded to
6. customa separately prepared (0° C.)
7. temperaturecooled mixture
8. stirringAfter stirring
9. customthe reaction at RT overnight
10. customquenched with ice cold water (20 mL)
11. additionfollowed by the addition of ethyl acetate (30 mL)
12. customThe layers were separated
13. extractionthe aqueous layer was extracted with ethyl acetate (3×20 mL)
14. washThe combined organic layers were washed with water (2×50 mL), brine (20 mL)
15. dry with materialdried (Na2SO4)
16. filtrationfiltered
17. concentrationThe filtrate was concentrated under vacuum
18. customthe crude product was purified by flash column chromatography (silica gel, DCM-methanol system as eluent)

ORD record

ord-54497d835ada410cb475b4db8d398d6a

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09399638B2