Sodium hydride → HCID 53577548, compound

To a solution of 3-methylpyridine-4-amine (1.23 g, 11.37 mmol, 1.2 eq) in DMF (5 mL) at 0° C. was added solid sodium hydride (60% suspension in mineral oil, 0.44 g, 18.49 mmol, 2.0 eq) and stirred for 1 h at room temperature. In a separate flask, to a solution of 5-bromothiophene-2-carboxylic acid (1.91 g, 9.25 mmol, 1.0 eq) in DCM (10 mL) was added oxalyl chloride (4.0 mL, 46.2 mmol, 5.0 eq) at 0° C. and then stirred at the same temperature for 2 h. The solvent and excess of oxalyl chloride were removed by evaporation under vacuum. The residue was dissolved in DMF (2 mL) and added to the above mixture at 0° C. and the resulting mixture was stirred at room temperature overnight. Water (10 mL) was added to the reaction followed by ethyl acetate (10 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (2×20 mL). The combined organic layers were washed with water (2×20 mL), brine (20 mL), dried (Na2SO4) and filtered. The filtrate was concentrated under vacuum and purified by column chromatography (silica gel, DCM:MeOH system) to afford 1.0 g of the desired product as a white solid. 1HNMR (400 MHz, CDCl3) δ 8.39 (d, J=5.5 Hz, 1H), 8.36 (s, 1H), 8.05 (d, J=5.5 Hz, 1H), 7.87 (s, 1H, D2O exchangeable), 7.40 (d, J=4.0 Hz, 1H), 7.09 (d, J=4.0 Hz, 1H), 2.29 (s, 3H); ESI-MS (m/z) 297, 299 [(MH)+ Br79,81].

1. stirringstirred at the same temperature for 2 h
2. customThe solvent and excess of oxalyl chloride were removed by evaporation under vacuum
3. dissolutionThe residue was dissolved in DMF (2 mL)
4. additionadded to the above mixture at 0° C.
5. stirringthe resulting mixture was stirred at room temperature overnight
6. additionWater (10 mL) was added to the reaction
7. customThe layers were separated
8. extractionthe aqueous layer was extracted with ethyl acetate (2×20 mL)
9. washThe combined organic layers were washed with water (2×20 mL), brine (20 mL)
10. dry with materialdried (Na2SO4)
11. filtrationfiltered
12. concentrationThe filtrate was concentrated under vacuum
13. custompurified by column chromatography (silica gel, DCM:MeOH system)

ORD record

ord-088911733cae42ffa919aa1165def4d7

Source dataset

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09169242B2