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

HRID 2374900Notes

Reaction equation

HRID 2374900 reaction equation
[CH3:1][O:2][C:3]1[CH:32]=[CH:31][CH:30]=[CH:29][C:4]=1[C:5]([NH:7][CH:8]([C:10]1[N:15]=[N:14][C:13]([NH:16][C:17]2[CH:22]=[C:21]([O:23][CH3:24])[C:20]([O:25][CH3:26])=[C:19]([O:27][CH3:28])[CH:18]=2)=[N:12][CH:11]=1)[CH3:9])=O.P(Cl)(Cl)(Cl)=O>ClCCCl.ClCCl.C([O-])([O-])=O.[Na+].[Na+]>[CH3:1][O:2][C:3]1[CH:32]=[CH:31][CH:30]=[CH:29][C:4]=1[C:5]1[N:15]2[C:10]([CH:11]=[N:12][C:13]([NH:16][C:17]3[CH:22]=[C:21]([O:23][CH3:24])[C:20]([O:25][CH3:26])=[C:19]([O:27][CH3:28])[CH:18]=3)=[N:14]2)=[C:8]([CH3:9])[N:7]=1

Participants

6

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 587119952-methoxy-N-(1-{3-[(3,4,5-trimethoxyphenyl)amino]-1,2,4-triazin-6-yl}ethyl)benzamide2×

Product 1

HCID 113047247-(2-methoxyphenyl)-5-methyl-N-(3,4,5-trimethoxyphenyl)imidazo[5,1-f][1,2,4]triazin-2-amineYield 19.8%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolventHCID 10340Sodium CarbonateSolvent

Procedure

To a solution of 2-methoxy-N-(1-{3-[(3,4,5-trimethoxyphenyl)amino]-1,2,4-triazin-6-yl}ethyl)benzamide (Intermediate 25) (27 mg, 0.06 mmol) in 1,2-dichloroethane (4 mL) was added phosphorus oxychloride (45 microL, 0.5 mmol). The mixture was heated to reflux for 4 hours. After cooling to room temperature, the mixture was diluted with DCM (150 mL) and aqueous (saturated) Na2CO3 (25 mL). The aqueous layer was extracted with dichloromethane (DCM) and the combined organic layers were washed with brine, dried over Na2SO4, concentrated under vacuum, and purified by reverse-phase HPLC to give 7-(2-methoxyphenyl)-5-methyl-N-(3,4,5-trimethoxyphenyl)imidazo[5,1-f][1,2,4]triazin-2-amine (0.005 g) as a yellow solid. 1H NMR (CDCl3): δ8.80 (s, 1H), 7.59 (dd J=7.51, 1.65 Hz, 1H), 7.44 (m, 1H), 7.00-7.07 (m, 3H), 6.84 (s, 1H), 3.78 (s, 6H), 3.59 (s, 6H), 2.63 (s, 3H). MS m/z 421 (M+1).

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 4 hours
  3. extractionThe aqueous layer was extracted with dichloromethane (DCM)
  4. washthe combined organic layers were washed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated under vacuum
  7. custompurified by reverse-phase HPLC

Sources & evidence

ORD record
ord-dd9497136afe448db5a4d4ca6d2d975c
Source dataset
uspto-grants-2008_12
Patent number
US07462614B2

Reaction notes

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