N-bromobutanimide → tert-Butyl 4-(3-amino-6-bromopyrazin-2-yl)-2-fluorobenzoate

HRID 595954Notes

Reaction equation

HRID 595954 reaction equation
[NH2:1][C:2]1[C:3]([C:8]2[CH:20]=[CH:19][C:11]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])=[C:10]([F:21])[CH:9]=2)=[N:4][CH:5]=[CH:6][N:7]=1.[Br:22]N1C(=O)CCC1=O>C(#N)C>[NH2:1][C:2]1[C:3]([C:8]2[CH:20]=[CH:19][C:11]([C:12]([O:14][C:15]([CH3:17])([CH3:18])[CH3:16])=[O:13])=[C:10]([F:21])[CH:9]=2)=[N:4][C:5]([Br:22])=[CH:6][N:7]=1

Participants

4

Reactant 2

HCID 67184N-bromobutanimideHCID 118046338tert-Butyl 4-(3-aminopyrazin-2-yl)-2-fluorobenzoate

Product 1

HCID 118045500tert-Butyl 4-(3-amino-6-bromopyrazin-2-yl)-2-fluorobenzoateYield 64.6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of tert-butyl 4-(3-aminopyrazin-2-yl)-2-fluorobenzoate (37.7 g, 130 mmol) in acetonitrile (800 mL) at 0° C. was added N-bromosuccinimide (23.19 g, 130 mmol) in one portion. The reaction was stirred at 0° C. for 2 h, then quenched with saturated NaHCO3 solution (200 mL) and stirred at 0° C. for 30 min. The mixture was diluted with water (300 mL) and extracted with EtOAc (3×250 mL). The combined organics were washed with water (200 mL) and brine (2×200 mL), dried over magnesium sulfate, filtered and concentrated. The crude material was purified using flash chromatography on silica gel (0 to 40% EtOAc in heptane over 40 min), giving tert-butyl 4-(3-amino-6-bromopyrazin-2-yl)-2-fluorobenzoate (30.9 g, 64%) as a solid. LCMS (m/z): 368/370 (MH+), 1.03 min; 1H NMR (400 MHz, DMSO-d6) δ ppm 8.14 (s, 1H) 7.97-7.74 (m, 1H) 7.62-7.39 (m, 2H) 6.64 (s, 2H) 1.54 (s, 9H).

Workup

  1. customquenched with saturated NaHCO3 solution (200 mL)
  2. stirringstirred at 0° C. for 30 min
  3. additionThe mixture was diluted with water (300 mL)
  4. extractionextracted with EtOAc (3×250 mL)
  5. washThe combined organics were washed with water (200 mL) and brine (2×200 mL)
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude material was purified
  10. customon silica gel (0 to 40% EtOAc in heptane over 40 min)

Sources & evidence

ORD record
ord-9394cd1462af44ada149d3dbd5b5477e
Source dataset
uspto-grants-2016_01
Patent number
US09242996B2

Reaction notes

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