Morpholine → 4-(3-(2,3-dichlorobenzyl)-2-methyl-7-nitro-3H-benzo[d]imidazol-5-yl)morpholine

HRID 44479Notes

Reaction equation

HRID 44479 reaction equation
Br[C:2]1[CH:3]=[C:4]([N+:21]([O-:23])=[O:22])[C:5]2[N:9]=[C:8]([CH3:10])[N:7]([CH2:11][C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([Cl:18])[C:13]=3[Cl:19])[C:6]=2[CH:20]=1.[NH:24]1[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.C([O-])([O-])=O.[Cs+].[Cs+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:19][C:13]1[C:14]([Cl:18])=[CH:15][CH:16]=[CH:17][C:12]=1[CH2:11][N:7]1[C:6]2[CH:20]=[C:2]([N:24]3[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)[CH:3]=[C:4]([N+:21]([O-:23])=[O:22])[C:5]=2[N:9]=[C:8]1[CH3:10]

Participants

7

Reactant 4

HCID 8083MorpholineHCID 10796Cesium carbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 669771206-bromo-1-(2,3-dichlorobenzyl)-2-methyl-4-nitro-1H-benzo[d]imidazole

Product 1

HCID 669766714-(3-(2,3-dichlorobenzyl)-2-methyl-7-nitro-3H-benzo[d]imidazol-5-yl)morpholineYield 48.4%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 6-bromo-1-(2,3-dichlorobenzyl)-2-methyl-4-nitro-1H-benzo[d]imidazole (1.69 g), morpholine (1.07 g), Pd2(dba)3 (376 mg), Cs2CO3 (2 g) and X-Phos (383 mg) in dioxane (80 mL) was degassed with nitrogen and then stirred at 80° C. for 3 h. When TLC showed complete consumption of starting material, the mixture was cooled to room temperature and the solvent was removed in-vacuo. The remaining residue was extracted with EtOAc. The organic layer was washed with brine, dried over anhydrous Na2SO4, filtered and concentrated in-vacuo. The residue was then purified by silica gel chromatography eluted with EtOAc:Petrolium ether=1:1 to afford the desired product as a yellow solid (831 mg, 48%). 1H NMR (300 MHz, CDCl3) δ ppm 2.62 (s, 3H), 3.18 (t, 4H, J=4.8 Hz), 3.87 (t, 4H, J=4.8 Hz), 5.41 (s, 2H), 6.28 (d, 1H, J=7.8 Hz), 6.86 (d, 1H, J=2.4 Hz), 7.08 (t, 1H, J=7.8 Hz), 7.46 (d, 1H, J=7.8 Hz), 7.79 (d, 1H, J=2.4 Hz); LC-MS: m/e=421 [M+1]+

Workup

  1. customwas degassed with nitrogen
  2. customconsumption of starting material
  3. temperaturethe mixture was cooled to room temperature
  4. customthe solvent was removed in-vacuo
  5. extractionThe remaining residue was extracted with EtOAc
  6. washThe organic layer was washed with brine
  7. dry with materialdried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in-vacuo
  10. customThe residue was then purified by silica gel chromatography
  11. washeluted with EtOAc

Sources & evidence

ORD record
ord-37b5f4f8890b4d00889a92407ee855ff
Source dataset
uspto-grants-2013_09
Patent number
US08541411B2

Reaction notes

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