Cesium carbonate → {4-[7-(2-Chloro-5-methoxy-phenyl)-5-methyl-benzo[1,2,4]triazin-3-ylamino]-phenyl}-(4-methyl-piperazin-1-yl)-methanone

HRID 273522Notes

Reaction equation

HRID 273522 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[C:10]1[CH:20]=[C:19]([CH3:21])[C:13]2[N:14]=[C:15]([NH2:18])[N:16]=[N:17][C:12]=2[CH:11]=1.Br[C:23]1[CH:28]=[CH:27][C:26]([C:29]([N:31]2[CH2:36][CH2:35][N:34]([CH3:37])[CH2:33][CH2:32]2)=[O:30])=[CH:25][CH:24]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[C:10]1[CH:20]=[C:19]([CH3:21])[C:13]2[N:14]=[C:15]([NH:18][C:23]3[CH:24]=[CH:25][C:26]([C:29]([N:31]4[CH2:36][CH2:35][N:34]([CH3:37])[CH2:33][CH2:32]4)=[O:30])=[CH:27][CH:28]=3)[N:16]=[N:17][C:12]=2[CH:11]=1

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 44643521-(4-Bromobenzoyl)-4-methylpiperazineHCID 248227537-(2-Chloro-5-methoxyphenyl)-5-methylbenzo[e][1,2,4]triazin-3-amine

Product 1

HCID 59837642{4-[7-(2-Chloro-5-methoxy-phenyl)-5-methyl-benzo[1,2,4]triazin-3-ylamino]-phenyl}-(4-methyl-piperazin-1-yl)-methanoneYield 58.2%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
70 °C

Procedure

In a dry 25 mL round bottom flask, 7-(2-chloro-5-methoxy-phenyl)-5-methyl-benzo[1,2,4]triazin-3-ylamine (0.282 g, 0.94 mmol, 1 equiv), (4-bromo-phenyl)-(4-methyl-piperazin-1-yl)-methanone (0.399 g, 1.41 mmol, 1.5 equiv), cesium carbonate (0.919 g, 2.82 mmol, 3 equiv), 4,5-bis(diphenylphosphino)-9,9-dimethyl xanthene (0.109 g, 0.188 mmol, 0.2 equiv) and tris(dibenzylideneacetone)dipalladium (0.086 g, 0.094 mmol, 0.1 equiv) were combined. The reactants were flushed with argon, diluted with dioxane (12 mL) and outfitted with reflux condenser. The reaction was heated to reflux for 18 hours, then filtered hot and solvents were evaporated. The residue was diluted with toluene and water (approx. 2:1), and the mixture was heated to 70° C. and stirred for 20 min. The contents were then poured into 250 mL separatory funnel and shaken. The resulting precipitate was filtered off, washed with water and dried to yield a yellow powder (0.275 g, 58% yield). MS (ESI+): m/z=504.1, LC retention time: 1.75 min.

Workup

  1. customThe reactants were flushed with argon
  2. additiondiluted with dioxane (12 mL)
  3. temperaturewith reflux condenser
  4. temperatureThe reaction was heated
  5. temperatureto reflux for 18 hours
  6. filtrationfiltered hot
  7. customsolvents were evaporated
  8. additionThe residue was diluted with toluene and water (approx. 2:1)
  9. additionThe contents were then poured into 250 mL separatory funnel
  10. stirringshaken
  11. filtrationThe resulting precipitate was filtered off
  12. washwashed with water
  13. customdried

Sources & evidence

ORD record
ord-26a7fcbaf54e431ca865fbca56d6db18
Source dataset
uspto-grants-2008_11
Patent number
US07456176B2

Reaction notes

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