Sodium Cyanide → N-benzyl-2-(1-(4-fluorobenzyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)isonicotinamide

HRID 714392Notes

Reaction equation

HRID 714392 reaction equation
[F:1][C:2]1[CH:24]=[CH:23][C:5]([CH2:6][N:7]2[C:11](=[O:12])[N:10]([C:13]3[CH:14]=[C:15]([CH:20]=[CH:21][N:22]=3)[C:16](OC)=[O:17])[CH:9]=[N:8]2)=[CH:4][CH:3]=1.[C-:25]#[N:26].[Na+]>C(N)C1C=CC=CC=1>[CH2:25]([NH:26][C:16](=[O:17])[C:15]1[CH:20]=[CH:21][N:22]=[C:13]([N:10]2[C:11](=[O:12])[N:7]([CH2:6][C:5]3[CH:23]=[CH:24][C:2]([F:1])=[CH:3][CH:4]=3)[N:8]=[CH:9]2)[CH:14]=1)[C:2]1[CH:24]=[CH:23][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 8929Sodium CyanideHCID 58247815methyl 2-(1-(4-fluorobenzyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)isonicotinate

Product 1

HCID 44553616N-benzyl-2-(1-(4-fluorobenzyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)isonicotinamideYield 6%

Reagents, catalysts & solvents 1

HCID 7504BenzylamineSolvent

Procedure

A solution of methyl 2-(1-(4-fluorobenzyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)isonicotinate and sodium cyanide (0.80 g, 1.43 mmol) in benzylamine (50 mL) was stirred at 100° C. for 23 hours and at 110° C. for 3 hours and concentrated in vacuo. The residue was dissolved in ethyl acetate (30 mL), washed with water (20 mL) and brine (20 mL). The organic solution was dried over anhydrous sodium sulphate, filtered and concentrated in vacuo to dryness. The residue was purified by column chromatography eluting with ethyl acetate in dichloromethane (0% to 50%) to give N-benzyl-2-(1-(4-fluorobenzyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)isonicotinamide as a colorless solid (0.29 g, 6%): mp 173-175° C.; 1H NMR (300 MHz, CDCl3) δ 8.56-8.55 (m, 1H), 8.49 (dd, J=5.1, 0.6 Hz, 1H), 8.41 (s, 1H), 7.73-7.70 (m, 1H), 7.32-7.22 (m, 7H), 7.00-6.95 (m, 3H), 4.90 (s, 2H), 4.60 (d, J=5.7 Hz, 2H); MS (ES+) m/z 403.9.

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThe residue was dissolved in ethyl acetate (30 mL)
  3. washwashed with water (20 mL) and brine (20 mL)
  4. dry with materialThe organic solution was dried over anhydrous sodium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo to dryness
  7. customThe residue was purified by column chromatography
  8. washeluting with ethyl acetate in dichloromethane (0% to 50%)

Sources & evidence

ORD record
ord-67563614a4954790a4a4aaabe0134323
Source dataset
uspto-grants-2015_11
Patent number
US09187426B2

Reaction notes

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