Methyl iodide → HCID 86681250, compound

HRID 1848275Notes

Reaction equation

HRID 1848275 reaction equation
[N:1]1[NH:2][N:3]=[N:4][C:5]=1[C:6]1[CH:26]=[CH:25][C:9]2[N:10]([CH2:13][C:14]3[CH:24]=[CH:23][C:17]4[N:18]=[C:19]([S:21][CH3:22])[S:20][C:16]=4[CH:15]=3)[CH:11]=[N:12][C:8]=2[CH:7]=1.[C:27]([O-])([O-])=O.[Cs+].[Cs+].IC>CN(C=O)C>[CH3:27][N:3]1[N:2]=[N:1][C:5]([C:6]2[CH:26]=[CH:25][C:9]3[N:10]([CH2:13][C:14]4[CH:24]=[CH:23][C:17]5[N:18]=[C:19]([S:21][CH3:22])[S:20][C:16]=5[CH:15]=4)[CH:11]=[N:12][C:8]=3[CH:7]=2)=[N:4]1

Participants

5

Reactant 3

HCID 6328Methyl iodide2×HCID 10796Cesium carbonateHCID 86681249HCID 86681249, compound

Product 1

HCID 86681250HCID 86681250, compoundYield 39%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a stirred mixture of 6-((5-(2H-tetrazol-5-yl)-1H-benzo[d]imidazol-1-yl)methyl)-2-(methylthio)benzo[d]thiazole (796 mg, 2.1 mmol), Cs2CO3 (673 mg, 2.1 mmol), and DMF (10 mL) was added iodomethane (129 μL, 2.1 mmol). The mixture was heated at 60° C. for 6 h. Additional iodomethane (30 μL, 0.5 mmol) was added and the mixture was stirred at 60° C. for an additional 4 h. The mixture was cooled to rt and partitioned between EtOAc (200 mL) and 0.5 M aq Na2CO3 (100 mL). The organic layer was separated and washed with brine (100 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography, eluting with 2% MeOH in CH2Cl2, to afford 6-((5-(2-methyl-2H-tetrazol-5-yl)-1H-benzo[d]imidazol-1-yl)methyl)-2-(methylthio)benzo[d]thiazole (318 mg, 39%) as a white solid. The regiochemistry of the alkylation was determined by 2-dimensional nuclear Overhauser effect (NOE) experiment. 1H NMR (500 MHz, DMSO-d6) δ 8.58 (s, 1H), 8.31 (s, 1H), 8.03 (s, 1H), 7.93 (dd, J=1.0, 8.4 Hz, 1H), 7.82 (d, J=8.4 Hz, 1H), 7.73 (d, J=8.6 Hz, 1H), 7.46 (dd, J=1.2, 8.4 Hz, 1H), 5.66 (s, 2H), 4.41 (s, 3H), 2.76 (s, 3H); LCMS (ESI) m/z 394 (M+H)+.

Workup

  1. temperatureThe mixture was cooled to rt
  2. custompartitioned between EtOAc (200 mL) and 0.5 M aq Na2CO3 (100 mL)
  3. customThe organic layer was separated
  4. washwashed with brine (100 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel flash chromatography
  9. washeluting with 2% MeOH in CH2Cl2

Sources & evidence

ORD record
ord-9f2882251799480a94fecc0271f4b842
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

Loading…