Sodium Bicarbonate → 2-methyl-6-morpholino-1-(naphthalen-1-ylmethyl)-1H-benzo[d]imidazol-4-ol

HRID 1749563Notes

Reaction equation

HRID 1749563 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:30].[Na+].C([O-])(O)=O.[Na+]>O.CO.OS(O)(=O)=O>[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[CH2:24][CH2:25][O:26][CH2:27][CH2:28]3)[CH:20]=[C:21]([OH:30])[C:4]=2[N:3]=1

Participants

7

Reactant 3

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

Product 1

HCID 669762582-methyl-6-morpholino-1-(naphthalen-1-ylmethyl)-1H-benzo[d]imidazol-4-ol

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 1118Sulfuric AcidSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 2-methyl-6-morpholino-1-(naphthalen-1-ylmethyl)-1H-benzo[d]imidazol-4-amine (842 mg) in H2O (20 mL), MeOH (1 mL) and conc. H2SO4 (3 mL) was added aqueous NaNO2 (344 mg) solution drop-wise at 0° C. The mixture was stirred at 0° C. for 15 min and then stirred at reflux temperature for 1 h. The mixture was cooled to room temperature and the pH neutralized with aqueous NaHCO3 solution. It was extracted with DCM (100 mL×3). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated in-vacuo. The residue was then purified by silica gel chromatography eluted with MeOH:DCM=1:60 and then by Prep-HPLC to afford crude desired product LC-MS: m/e=374 [M+1]+ containing an impurity that was removed by the two-step sequence described below.

Workup

  1. stirringstirred
  2. temperatureat reflux temperature for 1 h
  3. temperatureThe mixture was cooled to room temperature
  4. extractionIt was extracted with DCM (100 mL×3)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in-vacuo
  9. customThe residue was then purified by silica gel chromatography
  10. washeluted with MeOH

Sources & evidence

ORD record
ord-7f63609497804640b50c504cdd1a9f9c
Source dataset
uspto-grants-2015_10
Patent number
US09156797B2

Reaction notes

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