Pyridine → N-(5-Bromopyrazin-2-YL)-2,6-difluorobenzamide

HRID 1754340Notes

Reaction equation

[F:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([F:11])[C:3]=1[C:4](Cl)=[O:5].[NH2:12][C:13]1[CH:18]=[N:17][C:16]([Br:19])=[CH:15][N:14]=1.N1C=CC=CC=1>C(Cl)Cl>[Br:19][C:16]1[N:17]=[CH:18][C:13]([NH:12][C:4](=[O:5])[C:3]2[C:2]([F:1])=[CH:10][CH:9]=[CH:8][C:7]=2[F:11])=[N:14][CH:15]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a 0° C. cooled and stirred, solution of 2,6-difluorobenzoyl chloride (5.7 g, 36.2 mmol, 0.9 eq) in DCM (200 mL) was added drop wise a solution of 2-amino-5-bromopyrazine (7.0 g, 40.2 mmol, 1.0 eq) in DCM (50 mL) followed b pyridine (3.1 g, 36.2 mmol, 0.9 eq). The resulting mixture was stirred at room temperature for 15 h. The reaction was diluted with DCM (100 mL), and washed with 10% hydrochloric acid (100 mL), dried (Na2SO4) and filtered. The filtrate was concentrated under vacuum and the crude product was purified by flash column chromatography (silica gel, 10% ethyl acetate in hexane) to afford 6.0 g of the title product as a yellow solid. 1HNMR (400 MHz, CDCl3) δ 9.47 (s, 1H), 8.62 (s, 1H, D2O exchangeable), 8.24 (s, 1H), 7.53-7.45 (m, 1H), 7.03 (t, J=8.0 Hz, 2H); ESI-MS (m/z) 314, 316 [(MH)+ Br79,81].

Workup

stirringThe resulting mixture was stirred at room temperature for 15 h
washwashed with 10% hydrochloric acid (100 mL)
dry with materialdried (Na2SO4)
filtrationfiltered
concentrationThe filtrate was concentrated under vacuum
customthe crude product was purified by flash column chromatography (silica gel, 10% ethyl acetate in hexane)

Sources & evidence

ORD record: ord-85bcca9e7bd8445690e440f73c4b20a0
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09169242B2

Reaction notes

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