Potassium Carbonate → 6-((4-bromo-1H-imidazol-1-yl)methyl)-2-(methylthio)benzo[d]thiazole

HRID 1847993Notes

Reaction equation

HRID 1847993 reaction equation
Cl[CH2:2][C:3]1[CH:13]=[CH:12][C:6]2[N:7]=[C:8]([S:10][CH3:11])[S:9][C:5]=2[CH:4]=1.[Br:14][C:15]1[N:16]=[CH:17][NH:18][CH:19]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[Br:14][C:15]1[N:16]=[CH:17][N:18]([CH2:2][C:3]2[CH:13]=[CH:12][C:6]3[N:7]=[C:8]([S:10][CH3:11])[S:9][C:5]=3[CH:4]=2)[CH:19]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 866809946-(Chloromethyl)-2-(methylthio)benzo[d]thiazoleHCID 178418934HCID 178418934, compound

Product 1

HCID 866810186-((4-bromo-1H-imidazol-1-yl)methyl)-2-(methylthio)benzo[d]thiazoleYield 54%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred mixture of 6-(chloromethyl)-2-(methylthio)benzo[d]thiazole (0.2 g, 0.9 mmol) from Step 4 of this Example and 4-bromo-1H-imidazole (0.2 g, 1.3 mmol) in anhydrous DMF (3.0 mL) was added K2CO3 (0.37 g, 2.7 mmol). After stirred for 3 h at rt, the reaction mixture was partitioned between EtOAc (100 mL) and water (50 mL). The EtOAc layer was separated, washed with brine (50 ml), dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography eluting with a gradient of 30% EtOAc in hexanes to 100% EtOAc to afford 6-((4-bromo-1H-imidazol-1-yl)methyl)-2-(methylthio)benzo[d]thiazole (160 mg, 54%) as a yellow oil. The regiochemistry of the alkylation was determined by 2-dimensional nuclear Overhauser effect (NOE) experiment. 1H NMR (300 MHz, CDCl3) δ 7.85 (d, J=8.3 Hz, 1H), 7.54 (d, J=1.1 Hz, 1H), 7.45 (d, J=1.3 Hz, 1H), 7.24 (dd, J=1.7, 8.5 Hz, 1H), 6.88 (d, J=1.5 Hz, 1H), 5.17 (s, 2H), 2.80 (s, 3H). LCMS (ESI) m/z 340 and 342 (M+H)+.

Workup

  1. customthe reaction mixture was partitioned between EtOAc (100 mL) and water (50 mL)
  2. customThe EtOAc layer was separated
  3. washwashed with brine (50 ml)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel flash chromatography
  8. washeluting with a gradient of 30% EtOAc in hexanes to 100% EtOAc

Sources & evidence

ORD record
ord-3fee919635764c659fe7cd3b650d0a45
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

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