Morpholine → 4-(2-methyl-3-(naphthalen-1-ylmethyl)-7-nitro-3H-benzo[d]imidazol-5-yl)morpholine

HRID 44466Notes

Reaction equation

HRID 44466 reaction equation
Br[C:2]1[CH:3]=[C:4]([N+:23]([O-:25])=[O:24])[C:5]2[N:9]=[C:8]([CH3:10])[N:7]([CH2:11][C:12]3[C:21]4[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=4)[CH:15]=[CH:14][CH:13]=3)[C:6]=2[CH:22]=1.[NH:26]1[CH2:31][CH2:30][O:29][CH2:28][CH2:27]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]>[CH3:10][C:8]1[N:7]([CH2:11][C:12]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH:15]=[CH:14][CH:13]=2)[C:6]2[CH:22]=[C:2]([N:26]3[CH2:31][CH2:30][O:29][CH2:28][CH2:27]3)[CH:3]=[C:4]([N+:23]([O-:25])=[O:24])[C:5]=2[N:9]=1

Participants

7

Reactant 4

HCID 8083MorpholineHCID 10796Cesium carbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 669765616-bromo-2-methyl-1-(naphthalen-1-ylmethyl)-4-nitro-1H-benzo[d]imidazole

Product 1

HCID 669768494-(2-methyl-3-(naphthalen-1-ylmethyl)-7-nitro-3H-benzo[d]imidazol-5-yl)morpholineYield 60%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
80 °C

Procedure

A mixture of 6-bromo-2-methyl-1-(naphthalen-1-ylmethyl)-4-nitro-1H-benzo[d]imidazole (4.63 g), morpholine (3.05 g), Pd2(dba)3 (1.05 g), Cs2CO3 (5.72 g) and X-Phos (1.09 g) in dioxane (100 mL) was degassed with nitrogen and then stirred at 80° C. overnight. The mixture was cooled to room temperature and the solvent was removed 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 (2.8 g, 60%). 1H NMR (300 MHz, DMSO-d6) δ ppm 2.46 (s, 3H), 3.12 (t, 4H, J=4.8 Hz). 3.70 (t, 4H, J=4.8 Hz), 6.09 (s, 2H), 6.31 (d, 1H, J=7.5 Hz), 7.34 (t, 1H, J=7.5 Hz), 7.53 (d, 1H, J=2.1 Hz), 7.62-7.70 (m, 3H), 7.86 (d, 1H, J=8.1 Hz), 8.01 (d, 1H, J=7.5 Hz), 8.23 (d, 1H, J=8.1 Hz); LC-MS: m/e=403 [M+1]+.

Workup

  1. customwas degassed with nitrogen
  2. temperatureThe mixture was cooled to room temperature
  3. customthe solvent was removed in-vacuo
  4. customThe residue was then purified by silica gel chromatography
  5. washeluted with EtOAc

Sources & evidence

ORD record
ord-7acaff6609c149549f0f7f48d53100e7
Source dataset
uspto-grants-2013_09
Patent number
US08541411B2

Reaction notes

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