Diethyl Ether → 7-(2-methoxyethoxy)-2-(4-methoxyphenyl)-5H-pyrido[3,2-b]indole-4-carboxamide

HRID 2410721Notes

Reaction equation

HRID 2410721 reaction equation
[NH2:1][C:2]1[C:11]([C:12]2[CH:17]=[CH:16][C:15]([O:18][CH2:19][C:20]3C=CC=CC=3)=[CH:14][CH:13]=2)=[N:10][C:9]([C:26]2[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=2)=[CH:8][C:3]=1[C:4](OC)=[O:5].N([O-])=O.[Na+].[N-:38]=[N+]=[N-].[Na+].C([O:44][CH2:45]C)C>FC(F)(F)C(O)=O>[CH3:45][O:44][CH2:20][CH2:19][O:18][C:15]1[CH:16]=[CH:17][C:12]2[C:11]3[N:10]=[C:9]([C:26]4[CH:27]=[CH:28][C:29]([O:32][CH3:33])=[CH:30][CH:31]=4)[CH:8]=[C:3]([C:4]([NH2:38])=[O:5])[C:2]=3[NH:1][C:13]=2[CH:14]=1

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 33557Sodium AzideHCID 23668193Sodium NitriteHCID 66599449Methyl 3-amino-2-(4-(benzyloxy)phenyl)-6-(4-methoxyphenyl)isonicotinate

Product 1

HCID 666044017-(2-methoxyethoxy)-2-(4-methoxyphenyl)-5H-pyrido[3,2-b]indole-4-carboxamide

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

Methyl 3-amino-2-(4-(benzyloxy)phenyl)-6-(4-methoxyphenyl)isonicotinate (556 mg, 1.262 mmol) was dissolved in trifluoroacetic acid (6 mL) and the yellow solution cooled in an ice bath. Solid sodium nitrite (174 mg, 2.52 mmol) was added with stirring to give a dark red mixture. After 30 min, solid sodium azide (821 mg, 12.6 mmol) was added followed by diethyl ether (6 mL). The light red mixture was stirred in the ice bath for 30 min. The reaction was concentrated on the rotary evaporator and was then partitioned between EtOAc and sufficient saturated aqueous NaHCO3 solution (gas evolution) to neutralize the acid. The organic phase was separated, washed with brine, dried with sodium sulfate, and the solvent removed. Radial silica gel chromatography (step gradient elution with hexane containing 0 to 20% EtOAc) afforded the two major products as oils:

Workup

  1. temperaturethe yellow solution cooled in an ice bath
  2. customto give a dark red mixture
  3. concentrationThe reaction was concentrated on the rotary evaporator
  4. customwas then partitioned between EtOAc and sufficient saturated aqueous NaHCO3 solution (gas evolution)
  5. customThe organic phase was separated
  6. washwashed with brine
  7. dry with materialdried with sodium sulfate
  8. customthe solvent removed
  9. washRadial silica gel chromatography (step gradient elution with hexane containing 0 to 20% EtOAc)
  10. customafforded the two major products as oils

Sources & evidence

ORD record
ord-d3e830ec0d4e41ed955c17b866db0a6c
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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