Phosphorus oxychloride → 5-methyl-7-phenyl-N-(3,4,5-trimethoxyphenyl)imidazo[5,1-f][1,2,4]triazin-2-amine

HRID 2374866Notes

Reaction equation

HRID 2374866 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:13][C:14]2[N:15]=[N:16][C:17]([CH:20]([NH:22][C:23](=O)[C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[CH3:21])=[CH:18][N:19]=2)[CH:6]=[C:7]([O:11][CH3:12])[C:8]=1[O:9][CH3:10].P(Cl)(Cl)(Cl)=O>ClCCCl>[CH3:21][C:20]1[N:22]=[C:23]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[N:16]2[C:17]=1[CH:18]=[N:19][C:14]([NH:13][C:5]1[CH:4]=[C:3]([O:2][CH3:1])[C:8]([O:9][CH3:10])=[C:7]([O:11][CH3:12])[CH:6]=1)=[N:15]2

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 58711950N-(1-{3-[(3,4,5-trimethoxyphenyl)amino]-1,2,4-triazin-6-yl}ethyl)benzamide

Product 1

HCID 98867465-methyl-7-phenyl-N-(3,4,5-trimethoxyphenyl)imidazo[5,1-f][1,2,4]triazin-2-amineYield 9.4%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of N-(1-{3-[(3,4,5-trimethoxyphenyl)amino]-1,2,4-triazin-6-yl}ethyl)benzamide (150 mg, 0.38 mmol) in 1,2-dichloroethane (10 mL) was added phosphorus oxychloride (0.28 mL, 3.0 mmol). The mixture was heated to reflux for 24 hours. After cooling to room temperature, the excess phosphorus oxychloride was quenched with water and silica gel (0.5 g) was added to the reaction mixture, followed by evaporation of the volatiles under reduced pressure. The pre-adsorbed solids were loaded into a solid loading cartridge and subjected to a gradient elution using ethyl acetate:hexane (25:75) to ethyl acetate (100%) using a RediSep silica gel cartridge (4.2 g; ISCO). The appropriate fractions were combined and concentrated under reduced pressure to give 5-methyl-7-phenyl-N-(3,4,5-trimethoxyphenyl)imidazo[5,1-f][1,2,4]triazin-2-amine (0.014 g) as an off-white solid. 1H NMR (CDCl3): δ8.78 (s, 1H), 8.43 (d, J=6.9 Hz, 2H), 7.49-7.35 (m, 3H), 6.94 (s, 1H), 6.68 (s, 2H), 3.83 (s, 3H), 3.81 (s, 6H), 2.59 (s, 3H). MS m/z 392 (M+1).

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 24 hours
  3. customthe excess phosphorus oxychloride was quenched with water and silica gel (0.5 g)
  4. additionwas added to the reaction mixture
  5. customfollowed by evaporation of the volatiles under reduced pressure
  6. washsubjected to a gradient elution
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-379bcc175da2434aaaa02e455e4af0e5
Source dataset
uspto-grants-2008_12
Patent number
US07462614B2

Reaction notes

Loading…