3-Pyridinecarboxaldehyde → N-[3,5-bis(trifluoromethyl)benzyl]-2-methyl-N-[2-{1-[(pyridin-3-ylmethyl)amino]propyl}-5-(trifluoromethyl)benzyl]-2H-tetrazol-5-amine

HRID 390747Notes

Reaction equation

HRID 390747 reaction equation
[NH2:1][CH:2]([C:5]1[CH:33]=[CH:32][C:31]([C:34]([F:37])([F:36])[F:35])=[CH:30][C:6]=1[CH2:7][N:8]([CH2:15][C:16]1[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[C:18]([C:26]([F:29])([F:28])[F:27])[CH:17]=1)[C:9]1[N:10]=[N:11][N:12]([CH3:14])[N:13]=1)[CH2:3][CH3:4].[N:38]1[CH:43]=[CH:42][CH:41]=[C:40]([CH:44]=O)[CH:39]=1.[BH4-].[Na+]>C(O)C>[F:28][C:26]([F:29])([F:27])[C:18]1[CH:17]=[C:16]([CH:21]=[C:20]([C:22]([F:24])([F:23])[F:25])[CH:19]=1)[CH2:15][N:8]([CH2:7][C:6]1[CH:30]=[C:31]([C:34]([F:37])([F:36])[F:35])[CH:32]=[CH:33][C:5]=1[CH:2]([NH:1][CH2:44][C:40]1[CH:39]=[N:38][CH:43]=[CH:42][CH:41]=1)[CH2:3][CH3:4])[C:9]1[N:10]=[N:11][N:12]([CH3:14])[N:13]=1

Participants

5

Reactant 3

HCID 103713-PyridinecarboxaldehydeHCID 4311764Sodium borohydrideHCID 58966576N-[2-(1-aminopropyl)-5-(trifluoromethyl)benzyl]-N-[3,5-bis(trifluoromethyl)benzyl]-2-methyl-2H-tetrazol-5-amine

Product 1

HCID 58966425N-[3,5-bis(trifluoromethyl)benzyl]-2-methyl-N-[2-{1-[(pyridin-3-ylmethyl)amino]propyl}-5-(trifluoromethyl)benzyl]-2H-tetrazol-5-amineYield 864.6%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of N-[2-(1-aminopropyl)-5-(trifluoromethyl)benzyl]-N-[3,5-bis(trifluoromethyl)benzyl]-2-methyl-2H-tetrazol-5-amine (60.0 mg, 0.01 mmoles) in ethanol (0.85 mL) was added 3-pyridinecarboxaldehyde (26.0 mg, 0.122 mmoles) and the reaction mixture was stirred at room temperature for 18 hours. The reaction mixture was cooled to 0° C. and sodium borohydride (10.0 mg, 0.133 mmoles) was added in one portion. The reaction mixture was stirred in ice bath for 2 hours and then at room temperature for overnight. The reaction mixture was concentrated to remove ethanol and the residue was taken up in ethyl acetate and water. The aqueous layer was extracted with ethyl acetate (2×) and the combined organic layer was washed with brine, dried over sodium sulfate and concentrated. The crude product was purified using silica gel chromatography on the ISCO Combiflash system with a 1-9% methanol in dichloromethane gradient to yield the title compound (54.6 mg, 78% yield) as colorless gum.

Workup

  1. temperatureThe reaction mixture was cooled to 0° C.
  2. stirringThe reaction mixture was stirred in ice bath for 2 hours
  3. waitat room temperature for overnight
  4. concentrationThe reaction mixture was concentrated
  5. customto remove ethanol
  6. extractionThe aqueous layer was extracted with ethyl acetate (2×)
  7. washthe combined organic layer was washed with brine
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated
  10. customThe crude product was purified

Sources & evidence

ORD record
ord-35d1e7d6d93849f1a46496e6b420ffc3
Source dataset
uspto-grants-2013_02
Patent number
US08383660B2

Reaction notes

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