Sulfuric Acid → HCID 66976277, compound

HRID 539166Notes

Reaction equation

HRID 539166 reaction equation
[CH3:1][CH:2]([C:4]1[N:8]([CH2:9][C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH:13]=[CH:12][CH:11]=2)[C:7]2[CH:20]=[C:21]([N:25]3[CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)[CH:22]=[C:23](N)[C:6]=2[N:5]=1)[CH3:3].[OH:31]S(O)(=O)=O.N([O-])=O.[Na+].C([O-])(O)=O.[Na+]>O>[CH3:3][CH:2]([C:4]1[N:8]([CH2:9][C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH:13]=[CH:12][CH:11]=2)[C:7]2[CH:20]=[C:21]([N:25]3[CH2:26][CH2:27][O:28][CH2:29][CH2:30]3)[CH:22]=[C:23]([OH:31])[C:6]=2[N:5]=1)[CH3:1]

Participants

6

Reactant 4

HCID 1118Sulfuric AcidHCID 516892Sodium BicarbonateHCID 23668193Sodium NitriteHCID 66976923HCID 66976923, compound

Product 1

HCID 66976277HCID 66976277, compoundYield 27%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 2-(1-methylethyl)-6-(4-morpholinyl)-1-(1-naphthalenylmethyl)-1H-benzimidazol-4-amine (300 mg) in H2O (20 mL), and conc. H2SO4 (1 mL) was added aqueous NaNO2 (78 mg) solution dropwise at 0° C. The mixture was stirred at 0° C. for 15 min and then heated to reflux for 1 h. The mixture was cooled to room temperature and the pH neutralized with aqueous NaHCO3 solution. The solution was extracted with DCM (250 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 EtOAc:petroleum ether=1:1 to afford the desired product as a solid (80 mg, 27%). 1H NMR (300 MHz, DMSO-d6) δ ppm 1.21 (d, 6H, J=6.6 Hz), 2.91 (t, 4H, J=7.5 Hz), 3.03 (m, 1H, J=6.6 Hz), 3.64 (t, 4H, J=7.5 Hz), 5.89 (s, 2H), 6.27-6.34 (m, 3H), 7.32 (t, 1H, J=7.5 Hz), 7.59-7.70 (m, 2H), 7.83 (d, 1H, J=7.5 Hz), 8.00 (d, 1H, J=7.5 Hz), 8.27 (d, 1H, J=7.5 Hz), 9.55 (s, 1H); LC-MS: m/e=402 [M+1]+.

Workup

  1. temperatureheated
  2. temperatureto reflux for 1 h
  3. temperatureThe mixture was cooled to room temperature
  4. extractionThe solution was extracted with DCM (250 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 EtOAc

Sources & evidence

ORD record
ord-8394b4c02c56471ca82a58302c5f7e9e
Source dataset
uspto-grants-2014_10
Patent number
US08865912B2

Reaction notes

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