Sodium Bicarbonate → N-(4-(4-benzyl-2,6-dimethylphenyl)thiazol-2-yl)isonicotinamide

HRID 1465591Notes

Reaction equation

HRID 1465591 reaction equation
[Br-].[CH2:2]([Zn+])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.I[C:11]1[CH:16]=[C:15]([CH3:17])[C:14]([C:18]2[N:19]=[C:20]([NH:23][C:24](=[O:31])[C:25]3[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=3)[S:21][CH:22]=2)=[C:13]([CH3:32])[CH:12]=1.C([O-])(O)=O.[Na+]>C1COCC1>[CH2:2]([C:11]1[CH:12]=[C:13]([CH3:32])[C:14]([C:18]2[N:19]=[C:20]([NH:23][C:24](=[O:31])[C:25]3[CH:26]=[CH:27][N:28]=[CH:29][CH:30]=3)[S:21][CH:22]=2)=[C:15]([CH3:17])[CH:16]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 58442460N-(4-(4-iodo-2,6-dimethylphenyl)thiazol-2-yl)isonicotinamideHCID 178419772HCID 178419772, compound

Product 1

HCID 58442394N-(4-(4-benzyl-2,6-dimethylphenyl)thiazol-2-yl)isonicotinamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A THF solution of benzylzinc(II) bromide (4.0 mL, 2.0 mmol) was added to a degassed solution of N-(4-(4-iodo-2,6-dimethylphenyl)thiazol-2-yl)isonicotinamide (435 mg, 1.0 mmol) and tetrakistriphenylphosphine palladium (57.8 mg, 0.10 mmol) in THF (5.0 mL). The reaction mixture was heated at reflux for 16 h under N2 and then poured into saturated aqueous NaHCO3. The mixture was extracted with ethyl acetate, washed with brine, dried MgSO4, and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel to give N-(4-(4-benzyl-2,6-dimethylphenyl)thiazol-2-yl)isonicotinamide: 1H NMR (500 MHz, CDCl3 δ 8.70 (d, J=4.9 Hz, 2 H), 7.67 (d, J=4.9 Hz, 2 H), 7.33 (d, J=8.6 Hz, 2 H), 7.10-7.26 (m, 3 H), 6.80 (s, 1 H), 6.24 (s, 1 H), 3.86 (s, 2 H), 2.04 (s, 6 H); ESI-MS: m/z 399.9 (M+H)+.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 16 h under N2
  3. extractionThe mixture was extracted with ethyl acetate
  4. washwashed with brine, dried MgSO4
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by flash column chromatography on silica gel

Sources & evidence

ORD record
ord-065a3f18f9f34088b0f24f47e0c1c2b4
Source dataset
uspto-grants-2015_04
Patent number
US08999983B2

Reaction notes

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