Sodium Bromide → 4-bromo-2-methyl-6-(4-morpholinyl)-1-(1-naphthalenylmethyl)-1H-benzimidazole

HRID 44486Notes

Reaction equation

HRID 44486 reaction equation
[CH3:1][C:2]1[N:6]([CH2:7][C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[CH:11]=[CH:10][CH:9]=2)[C:5]2[CH:18]=[C:19]([N:23]3[CH2:28][CH2:27][O:26][CH2:25][CH2:24]3)[CH:20]=[C:21](N)[C:4]=2[N:3]=1.N([O-])=O.[Na+].[Na+].[Br-:34].C([O-])(O)=O.[Na+]>Br>[Br:34][C:21]1[C:4]2[N:3]=[C:2]([CH3:1])[N:6]([CH2:7][C:8]3[C:17]4[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=4)[CH:11]=[CH:10][CH:9]=3)[C:5]=2[CH:18]=[C:19]([N:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)[CH:20]=1

Participants

6

Reactant 4

HCID 253881Sodium BromideHCID 516892Sodium BicarbonateHCID 23668193Sodium NitriteHCID 669767452-methyl-6-morpholino-1-(naphthalen-1-ylmethyl)-1H-benzo[d]imidazol-4-amine

Product 1

HCID 669770504-bromo-2-methyl-6-(4-morpholinyl)-1-(1-naphthalenylmethyl)-1H-benzimidazoleYield 55%

Reagents, catalysts & solvents 1

HCID 260Hydrogen BromideSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 2-methyl-6-(4-morpholinyl)-1-(1-naphthalenylmethyl)-1H-benzimidazol-4-amine (prepared following the same procedure as for Example 2, 1.1 g, 3 mmol) in aqueous HBr (50 mL) was added aqueous NaNO2 (214 mg, 3.1 mmol) solution dropwise at 0-5° C. After addition the mixture was stirred at 0° C. for 5 minutes, it was added to another solution of NaBr (927 mg, 9 mmol) in aqueous HBr (50 mL) dropwise at 60° C. The resulting mixture was then heated to 80° C. for 30 minutes and then cooled to room temperature. The solution pH was neutralized with aqueous NaHCO3 (600 mL) and extracted with DCM (500 mL×3). The combined organic layers were concentrated in vacuum and the residue was purified by silica gel chromatography eluted with petroleum ether:EtOAc=1:1 to give the desired product (725 mg, 55%) as a white solid. 1H NMR (300 MHz, CDCl3) δ 2.55 ppm (s, 3H), 3.05 (t, 4H, J=4.8 Hz), 3.79 (t, 4H, J=4.8 Hz), 5.73 (s, 2H), 6.50 (dd, 1H, J=1.2, 7.5 Hz), 6.53 (d, 1H, J=1.8 Hz), 7.15 (d, 1H, J=1.8 Hz), 7.28 (t, 1H, J=7.5 Hz), 7.60-7.67 (m, 2H), 7.81 (d, 1H, J=8.4 Hz), 7.96 (d, 1H, J=7.5 Hz), 8.06 (d, 1H, J=8.4 Hz); LC-MS: m/e=436 [M+1]+.

Workup

  1. additionAfter addition the mixture
  2. temperatureThe resulting mixture was then heated to 80° C. for 30 minutes
  3. temperaturecooled to room temperature
  4. extractionextracted with DCM (500 mL×3)
  5. concentrationThe combined organic layers were concentrated in vacuum
  6. customthe residue was purified by silica gel chromatography
  7. washeluted with petroleum ether

Sources & evidence

ORD record
ord-a196e4da926d4d08914cabdfdcfc7aa0
Source dataset
uspto-grants-2013_09
Patent number
US08541411B2

Reaction notes

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