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 449219Notes

Reaction equation

HRID 449219 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>[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.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 9832798Tris(dibenzylideneacetone) dipalladiumCatalystHCID 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-893a02254e8c4e9493fa027e7b7984d8
Source dataset
uspto-grants-2013_07
Patent number
US08481536B2

Reaction notes

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