Cesium carbonate → [7-(2-Chloro-5-methoxy-phenyl)-5-methyl-benzo[1,2,4]triazin-3-yl]-[3-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-amine

HRID 449217Notes

Reaction equation

HRID 449217 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:24]=[C:25]([CH:34]=[CH:35][CH:36]=1)[O:26][CH2:27][CH2:28][N:29]1[CH2:33][CH2:32][CH2:31][CH2:30]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>[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1>[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:36]=[CH:35][CH:34]=[C:25]([O:26][CH2:27][CH2:28][N:29]4[CH2:30][CH2:31][CH2:32][CH2:33]4)[CH:24]=3)[N:16]=[N:17][C:12]=2[CH:11]=1

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 211452Pyrrolidine, 1-(2-(m-bromophenoxy)ethyl)-HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 248227537-(2-Chloro-5-methoxyphenyl)-5-methylbenzo[e][1,2,4]triazin-3-amine

Product 1

HCID 59837631[7-(2-Chloro-5-methoxy-phenyl)-5-methyl-benzo[1,2,4]triazin-3-yl]-[3-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-amineYield 65%

Reagents, catalysts & solvents 1

HCID 9832798Tris(dibenzylideneacetone) dipalladiumCatalyst

Procedure

In a dry 25 mL round bottom flask, 7-(2-chloro-5-methoxy-phenyl)-5-methyl-benzo[1,2,4]triazin-3-ylamine (0.113 g, 0.377 mmol, 1 equiv), 1-[2-(3-bromo-phenoxy)-ethyl]pyrrolidine (0.153 g, 0.565 mmol, 1.5 equiv), cesium carbonate (0.368 g, 1.13 mmol, 3 equiv), 4,5-bis(diphenylphosphino)-9,9-dimethyl xanthene (0.044 g, 0.0753 mmol, 0.2 equiv) and tris(dibenzylideneacetone) dipalladium (0.034 g, 0.0376 mmol, 0.1 equiv) were combined. The reactants were flushed with argon, diluted with dioxane (8 mL) and outfitted with reflux condenser. The reaction was heated to reflux for 18 hours, then filtered hot and the solvents were diluted with ethyl acetate and washed with brine. The brine layer was back extracted once with fresh ethyl acetate. The organic phases were combined and dried over sodium sulfate (Na2SO4). Filtration followed by evaporation and column chromatography (1:5 MeOH/DCM) provided desired product as a yellow powder (0.12 g, 65% yield). MS (ESI+): m/z=491.1, LC retention time: 2.94 min.

Workup

  1. customThe reactants were flushed with argon
  2. additiondiluted with dioxane (8 mL)
  3. temperaturewith reflux condenser
  4. temperatureThe reaction was heated
  5. temperatureto reflux for 18 hours
  6. filtrationfiltered hot
  7. additionthe solvents were diluted with ethyl acetate
  8. washwashed with brine
  9. extractionThe brine layer was back extracted once with fresh ethyl acetate
  10. dry with materialdried over sodium sulfate (Na2SO4)
  11. filtrationFiltration
  12. customfollowed by evaporation and column chromatography (1:5 MeOH/DCM)

Sources & evidence

ORD record
ord-7fe1c7c7873c4c7daf770553c6968978
Source dataset
uspto-grants-2013_07
Patent number
US08481536B2

Reaction notes

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