HCID 89717682, compound → HCID 89717934, compound

HRID 930200Notes

Reaction equation

HRID 930200 reaction equation
[C:1]([CH:3]([C:7]1[CH:12]=[CH:11][C:10]([C:13]2[N:14]=[N:15][N:16]([CH3:18])[N:17]=2)=[CH:9][C:8]=1[N+:19]([O-])=O)[C:4]([NH2:6])=[O:5])#[N:2]>CN(C=O)C.O.CO.[Zn]>[NH2:2][C:1]1[NH:19][C:8]2[C:7]([C:3]=1[C:4]([NH2:6])=[O:5])=[CH:12][CH:11]=[C:10]([C:13]1[N:14]=[N:15][N:16]([CH3:18])[N:17]=1)[CH:9]=2

Participants

6

Reactant 1

HCID 89717682HCID 89717682, compound

Product 1

HCID 89717934HCID 89717934, compoundYield 39.8%

Reagents, catalysts & solvents 4

HCID 23994ZincCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

Ferric chloride hexahydrate (2.82 g, 10.44 mmol) and zinc (2.276 g, 34.8 mmol) were added portionwise to a mixture of 2-cyano-2-(4-(2-methyl-2H-tetrazol-5-yl)-2-nitrophenyl)acetamide (1 g, 3.48 mmol) in DMF (8.71 mL) and water (8.71 mL) to give a yellow suspension which was heated to 100° C. for 1.25 hour. The mixture was then cooled to 20° C., diluted with MeOH (50.0 mL), filtered over Celite and concentrated under reduced pressure to ca. 20 mL (to remove most of the MeOH). Then the mixture was diluted with water (50 mL) and EtOAc (100 mL), stirred vigorously and filtered. The aqueous layer was extracted with EtOAc (2×50 mL) and the combined organic layers were washed with sat. NaHCO3 (50 mL) and brine (50 mL). The organic layer was dried over anh. MgSO4, filtered and concentrated to give 489 mg as a purple solid which was purified by flash chromatography to give 2-amino-6-(2-methyl-2H-tetrazol-5-yl)-1H-indole-3-carboxamide (356 mg, 39.7% yield) as a purple solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 4.38 (s, 3H) 6.57 (s, 2H) 7.01 (s, 2H) 7.61-7.69 (m, 2H) 7.81 (s, 1H) 10.77 (s, 1H); MS m/z 258.2 (M+H)+; HPLC ca. 78%, RT=1.34 minutes.

Workup

  1. customto give a yellow suspension which
  2. temperatureThe mixture was then cooled to 20° C.
  3. filtrationfiltered over Celite
  4. concentrationconcentrated under reduced pressure to ca. 20 mL (
  5. customto remove most of the MeOH)
  6. additionThen the mixture was diluted with water (50 mL) and EtOAc (100 mL)
  7. filtrationfiltered
  8. extractionThe aqueous layer was extracted with EtOAc (2×50 mL)
  9. washthe combined organic layers were washed with sat. NaHCO3 (50 mL) and brine (50 mL)
  10. dry with materialThe organic layer was dried over anh. MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customto give 489 mg as a purple solid which
  14. customwas purified by flash chromatography

Sources & evidence

ORD record
ord-905071e840eb4b1882d1fd3a30192318
Source dataset
uspto-grants-2016_03
Patent number
US09296744B2

Reaction notes

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