Dimethylformamide → 1-(4-Bromo-6-fluoro-1H-benzoimidazol-2-yl)-1H-pyrazole-4-carboxylic acid ethyl ester

HRID 408757Notes

Reaction equation

[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[N:8][N:9]([C:11](=[NH:22])[NH:12][C:13]2[C:18]([Br:19])=[CH:17][C:16]([F:20])=[CH:15][C:14]=2Br)[CH:10]=1)=[O:5])[CH3:2].C([O-])([O-])=O.[Cs+].[Cs+].CN(C=O)C>CCOC(C)=O.[Cu]I>[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[N:8][N:9]([C:11]2[NH:22][C:14]3[CH:15]=[C:16]([F:20])[CH:17]=[C:18]([Br:19])[C:13]=3[N:12]=2)[CH:10]=1)=[O:5])[CH3:2]

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of 1-[N-(2,6-dibromo-4-fluoro-phenyl)-carbamimidoyl]-1H-pyrazole-4-carboxylic acid ethyl ester (0.134 g, 0.290 mmol), CuI (6.00 mg, 0.0290 mmol), Cs2CO3 (0.464 g, 1.43 mmol), and DMF (2 mL) was heated to 80° C. for 1 h. The mixture was cooled to 23° C., diluted with EtOAc (3 mL), filtered through Celite®, and rinsed with EtOAc. The filtrate was washed with aqueous 1M HCl and water, dried (MgSO4), filtered, and concentrated under reduced pressure. Dichloromethane was added and the resulting precipitate was collected by filtration to yield the titled compound (17.0 mg, 17%). MS (ESI/CI): mass calcd. for C13H10BrFN4O2, 353.2; m/z found, 354.2 [M+H]+. 1H NMR (400 MHz, DMSO-d6): 13.86 (s, 1H), 8.95 (s, 1H), 8.36 (s, 1H), 7.45 (dd, J=9.6, 2.3 Hz, 1H), 7.32 (s, 1H), 4.30 (q, J=7.1 Hz, 2H), 1.33 (t, J=7.1 Hz, 3H).

Workup

temperatureThe mixture was cooled to 23° C.
filtrationfiltered through Celite®
washrinsed with EtOAc
washThe filtrate was washed with aqueous 1M HCl and water
dry with materialdried (MgSO4)
filtrationfiltered
concentrationconcentrated under reduced pressure
additionDichloromethane was added
filtrationthe resulting precipitate was collected by filtration

Sources & evidence

ORD record: ord-f47894928183453db1948110d0073aed
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08759345B2

Reaction notes

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