Triethylamine → 2-(3,4,5-Trimethoxyphenylamino)-6-[4-(4-fluorophenylcarbonyl)-aminophenyl]-pyrazine

HRID 16315Notes

Reaction equation

HRID 16315 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:13][C:14]2[CH:19]=[N:18][CH:17]=[C:16](OC3C=CC(N)=CC=3)[N:15]=2)[CH:6]=[C:7]([O:11][CH3:12])[C:8]=1[O:9][CH3:10].[F:28][C:29]1[CH:34]=[CH:33][C:32]([C:35](Cl)=[O:36])=[CH:31][CH:30]=1.C([N:40]([CH2:43][CH3:44])CC)C>O1CCOCC1>[CH3:12][O:11][C:7]1[CH:6]=[C:5]([NH:13][C:14]2[CH:19]=[N:18][CH:17]=[C:16]([C:7]3[CH:8]=[CH:3][C:4]([C:35]([C:32]4[CH:33]=[CH:34][C:29]([F:28])=[CH:30][CH:31]=4)=[O:36])=[CH:44][C:43]=3[NH2:40])[N:15]=2)[CH:4]=[C:3]([O:2][CH3:1])[C:8]=1[O:9][CH3:10]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 678794-Fluorobenzoyl chlorideHCID 593434392-(3,4,5-Trimethoxyphenylamino)-6-(4-aminophenyloxy)-pyrazine

Product 1

HCID 669125742-(3,4,5-Trimethoxyphenylamino)-6-[4-(4-fluorophenylcarbonyl)-aminophenyl]-pyrazineYield 50%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

Method LL. In a tube suitable for parallel synthesis, 2-(3,4,5-trimethoxyphenylamino)-6-(4-aminophenyloxy)-pyrazine (50 mg, 0.14 mmol) and 4-fluorophenylcarbonyl chloride (21 μL, 0.17 mmol) were stirred under nitrogen for 20 hours in dry dioxane (5 mL) in the presence of triethylamine (25 mL, 1.2 eq). The reaction mixture was evaporated to dryness, redissolved in 10 mL AcOEt, the solution washed (2×10 mL brine), dried, and purified by column chromatography (AcOEt) to give the title compound (33 mg). Yield: 50%. 1H NMR (250 MHz, DMSO-d6) δ 3.69 (s, 3H, [CH3O]4), 3.89 (s, 6H, [CH3O]3+5), 7.32 (s, 2H, Harom2′+6′), 7.44 (t, 2H, Harom 2″+6″, J=8.8 Hz), 7.98 (d, 2H, Harom 3+5, J=8.6 Hz), 8.10-8.21 (m, 4H, Harom 3″+5″ and Harom 2+6), 8.18 (s, 1H, HPz 5), 8.57 (s, 1H, HPz 3), 9.61 (s, 1H, NH), 10.50 (s, 1H, NHamide). m/z 475.2 [(M+H)+ calcd for C26H23FN4O4 474.2].

Workup

  1. customThe reaction mixture was evaporated to dryness
  2. dissolutionredissolved in 10 mL AcOEt
  3. washthe solution washed (2×10 mL brine)
  4. customdried
  5. custompurified by column chromatography (AcOEt)

Sources & evidence

ORD record
ord-bba561d25288450ba4b9f8c346145b1f
Source dataset
uspto-grants-2010_06
Patent number
US07737152B2

Reaction notes

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