Potassium Carbonate → methyl 1-((2-(methylthio)benzo[d]thiazol-6-yl)methyl)-1H-imidazole-4-carboxylate

HRID 1847997Notes

Reaction equation

HRID 1847997 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.[NH:14]1[CH:18]=[C:17]([C:19]([O:21][CH3:22])=[O:20])[N:16]=[CH:15]1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[CH3:11][S:10][C:8]1[S:9][C:5]2[CH:4]=[C:3]([CH2:2][N:14]3[CH:18]=[C:17]([C:19]([O:21][CH3:22])=[O:20])[N:16]=[CH:15]3)[CH:13]=[CH:12][C:6]=2[N:7]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 866809946-(Chloromethyl)-2-(methylthio)benzo[d]thiazoleHCID 178418785HCID 178418785, compound

Product 1

HCID 86681021methyl 1-((2-(methylthio)benzo[d]thiazol-6-yl)methyl)-1H-imidazole-4-carboxylateYield 19%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred mixture of 6-(chloromethyl)-2-(methylthio)benzo[d]thiazole (500 mg, 2.2 mmol) from Example 36 and methyl 4-imidazole carboxylate (400 mg, 3.3 mmol) in DMF (15 mL) was added K2CO3 (0.9 g, 6.5 mmol). After the mixture was stirred for 3 h at rt, it was partitioned between EtOAc (100 mL) and water (50 mL). The EtOAc layer was separated and washed with water (50 mL) and brine (50 mL), then dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography eluting with 2% MeOH in CH2Cl2 to afford methyl 1-((2-(methylthio)benzo[d]thiazol-6-yl)methyl)-1H-imidazole-4-carboxylate (130 mg, 19%) as a white solid. The regiochemistry of the alkylation was determined by 2-dimensional nuclear Overhauser effect (NOE) experiment. 1H NMR (300 MHz, DMSO-d6) δ 8.01 (d, J=0.9 Hz, 1H), 7.98 (d, J=1.1 Hz, 1H), 7.93 (d, J=0.9 Hz, 1H), 7.84 (d, J=8.3 Hz, 1H), 7.43 (dd, J=1.7, 8.3 Hz, 1H), 5.35 (s, 2H), 3.72 (s, 3H), 2.78 (s, 3H). LCMS (ESI) m/z 322 (M+H)+.

Workup

  1. customit was partitioned between EtOAc (100 mL) and water (50 mL)
  2. customThe EtOAc layer was separated
  3. washwashed with water (50 mL) and 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 2% MeOH in CH2Cl2

Sources & evidence

ORD record
ord-26d243ca22d947989b5d77dd21f2ff86
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

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