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Water → N-{4-(4-(5-Methoxypyrazin-2-ylthio)-2,6-dimethylphenyl)thiazol-2-yl}isonicotinamide

HRID 1465571
Notes
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Reaction equation

HRID 1465571 reaction equation
I[C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([C:9]2[N:10]=[C:11]([NH:14][C:15](=[O:22])[C:16]3[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=3)[S:12][CH:13]=2)=[C:4]([CH3:23])[CH:3]=1.[CH3:24][O:25][C:26]1[N:27]=[CH:28][C:29]([SH:32])=[N:30][CH:31]=1.C(=O)([O-])[O-].[K+].[K+].O>CN(C=O)C.[Cu](I)I>[CH3:24][O:25][C:26]1[N:27]=[CH:28][C:29]([S:32][C:2]2[CH:7]=[C:6]([CH3:8])[C:5]([C:9]3[N:10]=[C:11]([NH:14][C:15](=[O:22])[C:16]4[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=4)[S:12][CH:13]=3)=[C:4]([CH3:23])[CH:3]=2)=[N:30][CH:31]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 58442460N-(4-(4-iodo-2,6-dimethylphenyl)thiazol-2-yl)isonicotinamideHCID 178493800HCID 178493800, compound

Product 1

HCID 71586284N-{4-(4-(5-Methoxypyrazin-2-ylthio)-2,6-dimethylphenyl)thiazol-2-yl}isonicotinamideYield 75.1%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of N-(4-(4-iodo-2,6-dimethylphenyl)thiazol-2-yl)isonicotinamide (25-1, 173.5 mg, 0.40 mmol), 5-methoxypyrazine-2-thiol (25-2, 170 mg, 17.5 mmol), copper iodide (3.8 mg, 0.02 mmol), and potassium carbonate (165.3 mg, 1.2 mmol) in DMF (2 mL) was heated at 80° C. for 16 h. The solution was added with water and extracted with ethyl acetate. The organic layer was collected, dried over MgSO4(s), and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (20% EtOAc in hexanes as eluant) to provide N-{4-(4-(5-methoxypyrazin-2-ylthio)-2,6-dimethylphenyl)thiazol-2-yl}isonicotinamide (25, 135 mg) as yellow solids in 24% yield: 1H NMR (500 MHz, DMSO-d6) δ 8.77 (s, 2 H), 8.28 (s, 1 H), 8.18 (s, 1 H), 7.94-7.95 (m, 2 H), 7.14-7.21 (m, 3 H), 3.88 (s, 3 H), 2.03 (s, 6 H). ESI-MS: m/z 450.3 (M+H)+.

Workup

  1. extractionextracted with ethyl acetate
  2. customThe organic layer was collected
  3. dry with materialdried over MgSO4(s)
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by flash column chromatography on silica gel (20% EtOAc in hexanes as eluant)

Sources & evidence

ORD record
ord-9c138780b82d49a18383d9bb2d47c227
Source dataset
uspto-grants-2015_04
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08999983B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes