N-bromobutanimide → tert-Butyl (5-(bromomethyl)pyrazin-2-yl)carbamate

HRID 595901Notes

Reaction equation

[CH3:1][C:2]1[N:3]=[CH:4][C:5]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[N:6][CH:7]=1.C1C(=O)N([Br:23])C(=O)C1>C(Cl)(Cl)(Cl)Cl>[Br:23][CH2:1][C:2]1[N:3]=[CH:4][C:5]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:12])([CH3:14])[CH3:13])=[N:6][CH:7]=1

Participants

Conditions

Temperature: 85 °C

Procedure

A solution of tert-butyl 5-methylpyrazin-2-ylcarbamate (2.79 g, 13.33 mmol), NBS (2.61 g, 14.67 mmol) and AlBN (0.219 g, 1.33 mmol) in CCl4 (45 mL) was purged with Argon, then the solution was heated with 85° C. oil bath for 4 h. The reaction mixture was cooled to room temperature, concentrated and the residue was redissolved in EtOAc (˜50 mL), washed with dilute aqueous NaOH twice (10 mL 1 N NaOH diluted in 20 mL H2O), brine (30 mL), dried (Na2SO4) and concentrated. The residue was further purified by flash chromatography on silica gel eluted with gradient EtOAc/CH2Cl2 (0-30%) and tert-butyl 5-(bromomethyl)pyrazin-2-ylcarbamate was obtained in off-white solid. LCMS (m/z): 288.1/290.1 (MH+), 0.82 min; 1H NMR (400 MHz, CDCl3) δ ppm 9.26 (s, 1H), 8.32 (d, J=1.2 Hz, 1H), 7.62 (br. s., 1H), 4.56 (s, 2H), 1.56 (s, 9H).

Workup

temperatureThe reaction mixture was cooled to room temperature
concentrationconcentrated
dissolutionthe residue was redissolved in EtOAc (˜50 mL)
washwashed with dilute aqueous NaOH twice (10 mL 1 N NaOH diluted in 20 mL H2O), brine (30 mL)
dry with materialdried (Na2SO4)
concentrationconcentrated
customThe residue was further purified by flash chromatography on silica gel
washeluted with gradient EtOAc/CH2Cl2 (0-30%)

Sources & evidence

ORD record: ord-4443b3e244824b1f9506d440f4c513ac
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09242996B2

Reaction notes

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