Phosphorus oxychloride → HCID 11465304, compound

HRID 2374905Notes

Reaction equation

HRID 2374905 reaction equation
[F:1][C:2]([F:34])([F:33])[C:3]1[CH:32]=[CH:31][C:6]([C:7]([NH:9][CH:10]([C:12]2[N:17]=[N:16][C:15]([NH:18][C:19]3[CH:24]=[C:23]([O:25][CH3:26])[C:22]([O:27][CH3:28])=[C:21]([O:29][CH3:30])[CH:20]=3)=[N:14][CH:13]=2)[CH3:11])=O)=[CH:5][CH:4]=1.P(Cl)(Cl)(Cl)=O>ClCCCl.C(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+]>[CH3:11][C:10]1[N:9]=[C:7]([C:6]2[CH:31]=[CH:32][C:3]([C:2]([F:34])([F:33])[F:1])=[CH:4][CH:5]=2)[N:17]2[C:12]=1[CH:13]=[N:14][C:15]([NH:18][C:19]1[CH:24]=[C:23]([O:25][CH3:26])[C:22]([O:27][CH3:28])=[C:21]([O:29][CH3:30])[CH:20]=1)=[N:16]2

Participants

6

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 58711947HCID 58711947, compound2×

Product 1

HCID 11465304HCID 11465304, compoundYield 3%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolventHCID 10340Sodium CarbonateSolvent

Procedure

To a solution of 4-(trifluoromethyl)-N-(1-{3-[(3,4,5-trimethoxyphenyl)amino]-1,2,4-triazin-6-yl}ethyl)benzamide (Intermediate 27) (241 mg, 0.51 mmol) in 1,2-dichloroethane (20 mL) was added phosphorus oxychloride (0.37 mL, 4.0 mmol). The mixture was heated to reflux for 24 hours. After cooling to room temperature, the mixture was diluted with DCM and aqueous (saturated) Na2CO3. The aqueous was extracted with DCM and the combined organic layers were washed with brine, dried over Na2SO4, concentrated under vacuum and purified by silica gel chromatography to give 5-methyl-7-[4-(trifluoromethyl)phenyl]-N-(3,4,5-trimethoxyphenyl)imidazo[5,1-f][1,2,4]triazin-2-amine (0.007 g) as yellow solid. 1H NMR (CDCl3): δ8.85 (s, 1H), 8.86 (d J=8.24 Hz, 2H), 7.72 (d, J=8.24 Hz, 2H), 6.88 (m, 3H), 3.87 (s, 3H), 3.83 (s, 6H), 2.63 (s, 3H). MS m/z 459 (M+1).

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 24 hours
  3. extractionThe aqueous was extracted with DCM
  4. washthe combined organic layers were washed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated under vacuum
  7. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-aaa504630a83434aa8a9411566d756a7
Source dataset
uspto-grants-2008_12
Patent number
US07462614B2

Reaction notes

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