Sodium Hydroxide → 2-Amino-5-methyl-7-[3-(trifluoromethyl)phenyl]imidazo[5,1-f][1,2,4]triazin

HRID 2374936Notes

Reaction equation

HRID 2374936 reaction equation
[NH2:1][C:2]1[NH:7][C:6](=O)[C:5]([CH:9]([NH:11][C:12](=O)[C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:21])[F:20])[CH:14]=2)[CH3:10])=[N:4][N:3]=1.[OH-].[Na+]>O=P(Cl)(Cl)Cl>[NH2:1][C:2]1[N:7]=[CH:6][C:5]2=[C:9]([CH3:10])[N:11]=[C:12]([C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:21])[F:20])[CH:14]=3)[N:4]2[N:3]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 135984674HCID 135984674, compound2×

Product 1

HCID 587120012-Amino-5-methyl-7-[3-(trifluoromethyl)phenyl]imidazo[5,1-f][1,2,4]triazinYield 21.8%

Reagents, catalysts & solvents 1

HCID 24813Phosphorus oxychlorideSolvent

Conditions

Temperature
110 °C

Procedure

Crude N-[1-(3-amino-5-oxo-4,5-dihydro-1,2,4-triazin-6-yl)ethyl]-3-(trifluoromethyl)benzamide (Intermediate 42) (8.34 g, 25.5 mmol) was suspended in POCl3 (30 mL) and heated in a sealed tube at 110° C. for 2h. After the reaction had cooled to rt, the solution was carefully poured onto ice, neutralized with NaOH(aq) and extracted into EtOAc. The combined organic extracts were dried (MgSO4), filtered, and concentrated. Purification of the residue by chromatography afforded 2-amino-5-methyl-7-[3-(trifluoromethyl)phenyl]imidazo[5,1-f][1,2,4]triazin-4(3H-one (1.63 g) as a pale yellow solid. 1H NMR (DMSO-d6): δ10.91 (s, 1H), 8.75-8.71 (m, 1H), 8.66 (s, 1H), 7.77-7.68 (m, 2H), 6.25 (bs, 2H), 2.48 (s, 3H). MS m/z 308 (M−1).

Workup

  1. temperatureAfter the reaction had cooled to rt
  2. additionthe solution was carefully poured onto ice
  3. extractionextracted into EtOAc
  4. dry with materialThe combined organic extracts were dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification of the residue by chromatography

Sources & evidence

ORD record
ord-27bbd1fc5f3a4f3b84de9e47d7346ed1
Source dataset
uspto-grants-2008_12
Patent number
US07462614B2

Reaction notes

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