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

HRID 1812239Notes

Reaction equation

HRID 1812239 reaction equation
[Br:1][C:2]1[C:3]([NH2:9])=[N:4][CH:5]=[C:6]([Cl:8])[N:7]=1.[CH3:10][O:11][C:12]1[N:17]=[CH:16][C:15](B(O)O)=[CH:14][CH:13]=1.C(N(CC)C(C)C)(C)C>ClCCl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[Br:1][C:2]1[C:3]([NH:9][C:15]2[CH:16]=[N:17][C:12]([O:11][CH3:10])=[CH:13][CH:14]=2)=[N:4][CH:5]=[C:6]([Cl:8])[N:7]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 2734368(6-Methoxypyridin-3-yl)boronic acidHCID 104886093-Bromo-5-chloropyrazin-2-amine

Product 1

HCID 866470673-bromo-5-chloro-N-(6-methoxypyridin-3-yl)pyrazin-2-amineYield 17.5%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 6344DichloromethaneSolvent

Procedure

A mixture of 3-bromo-5-chloropyrazin-2-amine (624 mg, 2.99 mmol, Ark Phar. Inc), 6-methoxypyridin-3-ylboronic acid (1374 mg, 8.98 mmol, Combi. Blocks), copper (II) acetate (896 mg, 4.49 mmol, Aldrich, St. Louis, Mo.), and N,N-diisopropylethylamine (2.083 mL, 11.97 mmol, Aldrich, St. Louis, Mo.) in dichloromethane (20 mL) was stirred at room temperature for 48 h. The mixture was filtered through a pad of Celite® (diatomaceous earth) and washed with EtOAc. The solvent was removed in vacuo and the residue was purified by silica gel chromatography eluting with 10% EtOAc/hexanes to give 3-bromo-5-chloro-N-(6-methoxypyridin-3-yl)pyrazin-2-amine (165 mg, 0.523 mmol, 17.47% yield). 1H NMR (300 MHz, CDCl3) δ 3.95 (s, 3H) 6.79 (d, J=8.77 Hz, 1H) 6.92 (s, 1H) 7.77 (dd, J=8.84, 2.41 Hz, 1H) 8.01 (s, 1H) 8.29 (d, J=2.05 Hz, 1H). m/z (ESI, +ve ion) 316.9 (M+H)+.

Workup

  1. filtrationThe mixture was filtered through a pad of Celite® (diatomaceous earth)
  2. washwashed with EtOAc
  3. customThe solvent was removed in vacuo
  4. customthe residue was purified by silica gel chromatography
  5. washeluting with 10% EtOAc/hexanes

Sources & evidence

ORD record
ord-3f50b33047d6443e9b200382f4d941c9
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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