Hydrochloric Acid → HCID 11235155, compound

HRID 2374916Notes

Reaction equation

HRID 2374916 reaction equation
C([NH:4][C:5]1[CH:6]=[C:7]([CH:32]=[CH:33][CH:34]=1)[C:8]([NH:10][CH:11]([C:13]1[N:18]=[N:17][C:16]([NH:19][C:20]2[CH:25]=[C:24]([O:26][CH3:27])[C:23]([O:28][CH3:29])=[C:22]([O:30][CH3:31])[CH:21]=2)=[N:15][CH:14]=1)[CH3:12])=O)(=O)C.P(Cl)(Cl)(Cl)=O.Cl.[OH-].[Na+]>ClCCCl.CO>[NH2:4][C:5]1[CH:6]=[C:7]([C:8]2[N:18]3[C:13]([CH:14]=[N:15][C:16]([NH:19][C:20]4[CH:25]=[C:24]([O:26][CH3:27])[C:23]([O:28][CH3:29])=[C:22]([O:30][CH3:31])[CH:21]=4)=[N:17]3)=[C:11]([CH3:12])[N:10]=2)[CH:32]=[CH:33][CH:34]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 24813Phosphorus oxychloride2×HCID 587119463-(acetylamino)-N-(1-(3-[(3,4,5-trimethoxyphenyl)amino]-1,2,4-triazin-6-yl}ethyl)benzamide2×

Product 1

HCID 11235155HCID 11235155, compoundYield 2.1%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 887MethanolSolvent

Procedure

To a solution of 3-(acetylamino)-N-(1-{3-[(3,4,5-trimethoxyphenyl)amino]-1,2,4-triazin-6-yl}ethyl)benzamide (Intermediate 32) (110 mg, 0.24 mmol) in 1,2-dichloroethane (10 mL) was added phosphorous oxychloride (0.175 mL, 1.9 mmol). The mixture was refluxed for 6 hours, cooled to room temperature and more phosphorous oxychloride (0.10 mL, 1.0 mmol) was added. The reaction was then refluxed for 4 hours. After cooling to room temperature the reaction was diluted with methanol, then poured onto a mixture of ice and concentrated HCl. This mixture was brought to a pH of 8 by addition of concentrated aqueous NaOH. The mixture was then extracted with ethyl acetate, concentrated under vacuum and purified by reverse-phase HPLC to give 7-(3-aminophenyl)-5-methyl-N-(3,4,5-trimethoxyphenyl)imidazo[5,1-f][1,2,4]triazin-2-amine (2 mg) as a yellow solid. 1H NMR (CD3OD): δ9.00 (s, 1H), 7.60 (d, J=7.87 Hz, 1H), 7.54 (s, 1H), 7.21 (t, J=7.78 Hz, 1H), 7.09 (s, 2H), 6.79 (dd, J=7.87 and 2.01 Hz, 1H), 3.77 (s, 6H), 3.73 (s, 3H), 2.56 (s, 3H). MS m/z 406 (M+1).

Workup

  1. temperatureThe mixture was refluxed for 6 hours
  2. temperatureThe reaction was then refluxed for 4 hours
  3. temperatureAfter cooling to room temperature the reaction
  4. extractionThe mixture was then extracted with ethyl acetate
  5. concentrationconcentrated under vacuum
  6. custompurified by reverse-phase HPLC

Sources & evidence

ORD record
ord-07ceeb747de3406387cc421d409e5f7f
Source dataset
uspto-grants-2008_12
Patent number
US07462614B2

Reaction notes

Loading…