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

HRID 1843816Notes

Reaction equation

HRID 1843816 reaction equation
[Br-].[O:2]([C:4]1[CH:11]=[CH:10][C:7]([CH2:8][Zn+])=[CH:6][CH:5]=1)[CH3:3].I[C:13]1[CH:18]=[C:17]([CH3:19])[C:16]([C:20]2[N:21]=[C:22]([NH:25][C:26](=[O:33])[C:27]3[CH:32]=[CH:31][N:30]=[CH:29][CH:28]=3)[S:23][CH:24]=2)=[C:15]([CH3:34])[CH:14]=1.C([O-])(O)=O.[Na+]>C1COCC1>[CH3:3][O:2][C:4]1[CH:11]=[CH:10][C:7]([CH2:8][C:13]2[CH:14]=[C:15]([CH3:34])[C:16]([C:20]3[N:21]=[C:22]([NH:25][C:26](=[O:33])[C:27]4[CH:28]=[CH:29][N:30]=[CH:31][CH:32]=4)[S:23][CH:24]=3)=[C:17]([CH3:19])[CH:18]=2)=[CH:6][CH:5]=1

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 58442460N-(4-(4-iodo-2,6-dimethylphenyl)thiazol-2-yl)isonicotinamideHCID 178490611HCID 178490611, compound

Product 1

HCID 53389652N-(4-(4-(4-methoxybenzyl)-2,6-dimethylphenyl)thiazol-2-yl)isonicotinamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A THF solution of 4-methoxylbenzylzinc(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 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-(4-methoxybenzyl)-2,6-dimethylphenyl)thiazol-2-yl)isonicotinamide: 1H NMR (500 MHz, CDCl3) δ 8.69 (d, J=5.2 Hz, 2 H), 7.66 (d, J=4.9 Hz, 2 H), 7.11 (d, J=8.4 Hz, 2 H), 6.86 (d, 2 H), 6.80 (s, 1 H), 6.75 (s, 2 H), 3.80 (s, 2 H), 3.78 (s, 2 H), 1.98(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-1175a0f5ac3d4d6c83e1381d541e1aa1
Source dataset
uspto-grants-2015_02
Patent number
US08946268B2

Reaction notes

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