Diisopropylethylamine → 3-bromo-5-chloro-N-(5-fluoro-6-methoxypyridin-3-yl)pyrazin-2-amine

HRID 1621825Notes

Reaction equation

HRID 1621825 reaction equation
[Br:1][C:2]1[C:3]([NH2:9])=[N:4][CH:5]=[C:6]([Cl:8])[N:7]=1.[F:10][C:11]1[CH:12]=[C:13](B(O)O)[CH:14]=[N:15][C:16]=1[O:17][CH3:18].C(N(CC)C(C)C)(C)C>ClCCl.O.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[Br:1][C:2]1[C:3]([NH:9][C:13]2[CH:14]=[N:15][C:16]([O:17][CH3:18])=[C:11]([F:10])[CH:12]=2)=[N:4][CH:5]=[C:6]([Cl:8])[N:7]=1

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 104886093-Bromo-5-chloropyrazin-2-amineHCID 44717400(5-Fluoro-6-methoxypyridin-3-yl)boronic acid

Product 1

HCID 866470653-bromo-5-chloro-N-(5-fluoro-6-methoxypyridin-3-yl)pyrazin-2-amineYield 17.5%

Reagents, catalysts & solvents 3

HCID 8895Cupric acetateCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 3-bromo-5-chloropyrazin-2-amine (780 mg, 3.74 mmol, Ark Phar. Inc., Libertyville, Ill.), 5-fluoro-6-methoxypyridin-3-ylboronic acid (1919 mg, 11.23 mmol, Anichem), N,N-diisopropylethylamine (1.953 mL, 11.23 mmol, Aldrich, St. Louis, Mo.) and copper (II) acetate (1.12 g, 5.61 mmol, Aldrich, St. Louis, Mo.) in dichloromethane (30 mL) was stirred at room temperature for 72 h. The reaction mixture was diluted with water (20 mL) and extracted with EtOAc (2×40 mL). The combined organic extracts were washed with saturated NaCl (20 mL) and dried over Na2SO4. The solution was filtered and concentrated in vacuo to give the crude material as a light-yellow solid. The crude product was purified by silica gel chromatography, eluting with 20% EtOAc/hexanes to give 3-bromo-5-chloro-N-(5-fluoro-6-methoxypyridin-3-yl)pyrazin-2-amine (218 mg, 0.654 mmol, 17.47% yield). 1H NMR (300 MHz, CDCl3) δ 4.03 (s, 3H) 7.00 (s, 1H) 7.82 (dd, J=11.25, 1.75 Hz, 1H) 8.04 (d, J=9.06 Hz, 2H). m/z (ESI, +ve ion) 331.9 (M+H)+.

Workup

  1. extractionextracted with EtOAc (2×40 mL)
  2. washThe combined organic extracts were washed with saturated NaCl (20 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationThe solution was filtered
  5. concentrationconcentrated in vacuo
  6. customto give the crude material as a light-yellow solid
  7. customThe crude product was purified by silica gel chromatography
  8. washeluting with 20% EtOAc/hexanes

Sources & evidence

ORD record
ord-180087a051004d2184c66c5b0eeee21b
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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