Sodium Carbonate → 4-(4-bromo-1-(2,3-dichlorobenzyl)-2-methyl-1H-benzo[d]imidazol-6-yl)morpholine

HRID 539170Notes

Reaction equation

HRID 539170 reaction equation
N([O-])=O.[Na+].[Cl:5][C:6]1[C:11]([Cl:12])=[CH:10][CH:9]=[CH:8][C:7]=1[CH2:13][N:14]1[C:18]2[CH:19]=[C:20]([N:24]3[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)[CH:21]=[C:22](N)[C:17]=2[N:16]=[C:15]1[CH3:30].[Na+].[Br-:32].C([O-])([O-])=O.[Na+].[Na+]>O.Br>[Br:32][C:22]1[C:17]2[N:16]=[C:15]([CH3:30])[N:14]([CH2:13][C:7]3[CH:8]=[CH:9][CH:10]=[C:11]([Cl:12])[C:6]=3[Cl:5])[C:18]=2[CH:19]=[C:20]([N:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)[CH:21]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 253881Sodium BromideHCID 23668193Sodium NitriteHCID 669769571-[(2,3-dichlorophenyl)methyl]-2-methyl-6-(4-morpholinyl)-1H-benzimidazol-4-amine

Product 1

HCID 669767924-(4-bromo-1-(2,3-dichlorobenzyl)-2-methyl-1H-benzo[d]imidazol-6-yl)morpholineYield 44%

Reagents, catalysts & solvents 2

HCID 260Hydrogen BromideSolvent2×HCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

A solution of NaNO2 (0.37 g, 5.4 mmol) in water (0.5 ml) was added to a solution of 1-[(2,3-dichlorophenyl)methyl]-2-methyl-6-(4-morpholinyl)-1H-benzimidazol-4-amine (prepared following the same procedure as for Example 7, 2.0 g, 5 mmol) in HBr (60 mL) at 0-5° C. and stirred for 15 min. The mixture was added dropwise to a solution of NaBr (1.5 g, 15 mmol) in HBr (60 ml) at 60° C., and then heated to 80° C. for 30 min. The mixture was cooled to rt and poured into a Na2CO3 solution (200 ml). The mixture was extracted with DCM (100 mL×3). The combined organic layers were dried over Na2SO4, filtered, concentrated. The residue was purified by silica gel chromatography eluted with EtOAc to give the product (1 g, 44%), as a white solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 2.39 (s, 3H), 3.06 (t, 4H, J=4.8 Hz), 3.70 (t, 4H, J=4.8 Hz), 5.53 (s, 2H), 6.31 (dd, 1H, J=1.2, 7.8 Hz), 7.02 (d, 1H, J=2.1 Hz), 7.09 (d, 1H, J=2.1 Hz), 7.26 (t, 1H, J=7.8 Hz), 7.60 (dd, 1H, J=1.2 Hz, 7.8 Hz); LC-MS: m/e=455 [M+1]+.

Workup

  1. customprepared
  2. customat 0-5° C.
  3. temperatureThe mixture was cooled to rt
  4. extractionThe mixture was extracted with DCM (100 mL×3)
  5. dry with materialThe combined organic layers were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel chromatography
  9. washeluted with EtOAc

Sources & evidence

ORD record
ord-73c540f76cb54b62955a94c4745a7d9f
Source dataset
uspto-grants-2014_10
Patent number
US08865912B2

Reaction notes

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