Cesium carbonate → 5-[7-(2-Chloro-5-methoxy-phenyl)-5-methyl-benzo[1,2,4]triazin-3-ylamino]-pyridine-2-carboxylic acid (2-pyrrolidin-1-yl-ethyl)-amide

HRID 273523Notes

Reaction equation

HRID 273523 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.[N:22]1([CH2:27][CH2:28][NH:29][C:30]([C:32]2[CH:37]=[CH:36][C:35](Br)=[CH:34][N:33]=2)=[O:31])[CH2:26][CH2:25][CH2:24][CH2:23]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].CO.C(Cl)Cl>[N:22]1([CH2:27][CH2:28][NH:29][C:30]([C:32]2[CH:37]=[CH:36][C:35]([NH:18][C:15]3[N:16]=[N:17][C:12]4[CH:11]=[C:10]([C:3]5[CH:4]=[C:5]([O:8][CH3:9])[CH:6]=[CH:7][C:2]=5[Cl:1])[CH:20]=[C:19]([CH3:21])[C:13]=4[N:14]=3)=[CH:34][N:33]=2)=[O:31])[CH2:26][CH2:25][CH2:24][CH2:23]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 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-amineHCID 587487285-Bromo-pyridine-2-carboxylic acid (2-pyrrolidin-1-yl-ethyl)-amide

Product 1

HCID 598377865-[7-(2-Chloro-5-methoxy-phenyl)-5-methyl-benzo[1,2,4]triazin-3-ylamino]-pyridine-2-carboxylic acid (2-pyrrolidin-1-yl-ethyl)-amideYield 55%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 21226129Dichloromethane methanolSolvent

Procedure

In a dry 25 mL round bottom flask, 7-(2-chloro-5-methoxy-phenyl)-5-methyl-benzo[1,2,4]triazin-3-ylamine (0.090 g, 0.299 mmol, 1 equiv), 5-bromo-pyridine-2-carboxylic acid (2-pyrrolidin-1-yl-ethyl)-amide (0.134 g, 0.449 mmol, 1.5 equiv), cesium carbonate (0.293 g, 0.899 mmol, 3 equiv), 4,5-bis(diphenylphosphino)-9,9-dimethyl xanthene (0.035 g, 0.059 mmol, 0.2 equiv) and tris(dibenzylideneacetone)dipalladium (0.027 g, 0.0299 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 24 hours, then sonicated and slowly diluted with water. The resulting orange precipitate was filtered and dried. Column chromatography (1:5 MeOH/DCM) provided desired product as a yellow solid (0.085 g, 55% yield).

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 24 hours
  6. customsonicated
  7. additionslowly diluted with water
  8. filtrationThe resulting orange precipitate was filtered
  9. customdried

Sources & evidence

ORD record
ord-d7144d0f5fe447adb6d51947dec2f1b4
Source dataset
uspto-grants-2008_11
Patent number
US07456176B2

Reaction notes

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