benzyl-{2-[2-(3,5-dimethylphenyl)-5-isocyanato-1H-indol-3-yl]ethyl}-(4-Pyridin-3-yl-Butyl)amine → 1-[3-{2-[benzyl-(4-pyridin-3-yl-butyl)-amino]ethyl}-2-(3,5-dimethylphenyl)-1H-indol-5-yl]-1,4-dihydrotetrazol-5-one

HRID 1532374Notes

Reaction equation

HRID 1532374 reaction equation
[N-:1]=[N+:2]=[N-:3].[Al+3].[N-]=[N+]=[N-].[N-]=[N+]=[N-].[CH2:11]([N:18]([CH2:29][CH2:30][C:31]1[C:39]2[C:34](=[CH:35][CH:36]=[C:37]([N:40]=[C:41]=[O:42])[CH:38]=2)[NH:33][C:32]=1[C:43]1[CH:48]=[C:47]([CH3:49])[CH:46]=[C:45]([CH3:50])[CH:44]=1)[CH2:19][CH2:20][CH2:21][CH2:22][C:23]1[CH:24]=[N:25][CH:26]=[CH:27][CH:28]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>>[CH2:11]([N:18]([CH2:19][CH2:20][CH2:21][CH2:22][C:23]1[CH:24]=[N:25][CH:26]=[CH:27][CH:28]=1)[CH2:29][CH2:30][C:31]1[C:39]2[C:34](=[CH:35][CH:36]=[C:37]([N:40]3[C:41](=[O:42])[NH:3][N:2]=[N:1]3)[CH:38]=2)[NH:33][C:32]=1[C:43]1[CH:44]=[C:45]([CH3:50])[CH:46]=[C:47]([CH3:49])[CH:48]=1)[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Participants

3

Reactant 2

HCID 21249908benzyl-{2-[2-(3,5-dimethylphenyl)-5-isocyanato-1H-indol-3-yl]ethyl}-(4-Pyridin-3-yl-Butyl)amineHCID 21652180Aluminum azide

Product 1

HCID 1357385301-[3-{2-[benzyl-(4-pyridin-3-yl-butyl)-amino]ethyl}-2-(3,5-dimethylphenyl)-1H-indol-5-yl]-1,4-dihydrotetrazol-5-oneYield 44.7%

Procedure

To a solution of freshly prepared aluminum azide (0.6 mmol in 6 mL dry tetrahydrofuran) was added 120 mg benzyl-{2-[2-(3,5-dimethylphenyl)-5-isocyanato-1H-indol-3-yl]ethyl}-(4-pyridin-3-yl-butyl)amine and the mixture heated to reflux on an oil bath. After 20 hours, the mixture was cooled to room temperature concentrated poured into a mixture of 1M sodium potassium tartarate and ice, stirred vigorously for 40 minutes then partitioned between ethyl acetate and water. The organic portion was washed successively with 1M sodium potassium tartarate, water and brine then dried over sodium sulfate. Purification of the concentrate by flash chromatography on silica gel (methylene chloride:methanol, 88:12) gave the title compound (58 mg).

Workup

  1. temperaturethe mixture heated
  2. temperatureto reflux on an oil bath
  3. concentrationconcentrated
  4. additionpoured into a mixture of 1M sodium potassium tartarate and ice
  5. customthen partitioned between ethyl acetate and water
  6. washThe organic portion was washed successively with 1M sodium potassium tartarate, water and brine
  7. dry with materialthen dried over sodium sulfate
  8. customPurification of the
  9. concentrationconcentrate by flash chromatography on silica gel (methylene chloride:methanol, 88:12)

Sources & evidence

ORD record
ord-4ac14f73edd94200a95f09a67bce525b
Source dataset
uspto-grants-2001_03
Patent number
US06200957B1

Reaction notes

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