N-bromobutanimide → 3-(4-Bromo-2-fluoro-phenylamino)-5-formylaminomethyl-pyrazine-2-carboxylic acid methyl ester

HRID 2064012Notes

Reaction equation

[CH3:1][O:2][C:3]([C:5]1[C:10]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([Si](C)(C)C)=[CH:14][C:13]=2[F:22])=[N:9][C:8]([CH2:23][NH:24][CH:25]=[O:26])=[CH:7][N:6]=1)=[O:4].C1C(=O)N([Br:34])C(=O)C1>ClCCl.C(OCC)(=O)C>[CH3:1][O:2][C:3]([C:5]1[C:10]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([Br:34])=[CH:14][C:13]=2[F:22])=[N:9][C:8]([CH2:23][NH:24][CH:25]=[O:26])=[CH:7][N:6]=1)=[O:4]

Participants

Conditions

Temperature: -30 °C

Procedure

To a −30° C. solution of 3-(2-fluoro-4-trimethylsilanyl-phenylamino)-5-formylaminomethyl-pyrazine-2-carboxylic acid methyl ester (1.84 g, 4.89 mmol) in dichloromethane (50 mL) under N2 was added NBS (0.96 g, 5.38 mmol, 1.1 eq.), and the reaction mixture was stirred at −30° C. for 3 h. More NBS (0.96 g, 5.38 mmol, 1.1 eq.) was added, and the reaction mixture was allowed to stand at 0° C. for 18 h. The reaction mixture was diluted with ethyl acetate (250 mL). The organic layer was washed with saturated aqueous solution of sodium bicarbonate, water and brine, dried (Na2SO4), filtered and concentrated in vacuo. The crude material was triturated with methanol to afford the desired product as a yellow solid (1.50 g, 80.1%). LCMS (method C): RT=2.51 min, [M+H]+=383/384.

Workup

waitto stand at 0° C. for 18 h
washThe organic layer was washed with saturated aqueous solution of sodium bicarbonate, water and brine
dry with materialdried (Na2SO4)
filtrationfiltered
concentrationconcentrated in vacuo
customThe crude material was triturated with methanol

Sources & evidence

ORD record: ord-d61c3f356d2a49c58a90532ca8e12530
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08288408B2

Reaction notes

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