Cesium carbonate → 2-((2-Chloro-5-cyano-3-(4-methyl-2-oxopiperazin-1-yl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

HRID 921869Notes

Reaction equation

HRID 921869 reaction equation
Cl[C:2]1[N:7]=[C:6]([N:8]([CH:18]2[CH2:20][CH2:19]2)[CH2:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=2)[C:5]2=[N:21][CH:22]=[C:23]([C:24]#[N:25])[N:4]2[N:3]=1.[NH2:26][C:27]1[CH:28]=[C:29]([CH:32]=[C:33]([N:36]2[CH2:41][CH2:40][N:39]([CH3:42])[CH2:38][C:37]2=[O:43])[C:34]=1[Cl:35])[C:30]#[N:31].C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2]>[Cl:35][C:34]1[C:33]([N:36]2[CH2:41][CH2:40][N:39]([CH3:42])[CH2:38][C:37]2=[O:43])=[CH:32][C:29]([C:30]#[N:31])=[CH:28][C:27]=1[NH:26][C:2]1[N:7]=[C:6]([N:8]([CH:18]2[CH2:20][CH2:19]2)[CH2:9][C:10]2[CH:11]=[CH:12][C:13]([O:16][CH3:17])=[CH:14][CH:15]=2)[C:5]2=[N:21][CH:22]=[C:23]([C:24]#[N:25])[N:4]2[N:3]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 867084772-Chloro-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrileHCID 89922410HCID 89922410, compound

Product 1

HCID 899225422-((2-Chloro-5-cyano-3-(4-methyl-2-oxopiperazin-1-yl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrileYield 97.1%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 2-chloro-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (40 mg, 0.113 mmol), 3-amino-4-chloro-5-(4-methyl-2-oxopiperazin-1-yl)benzonitrile (28 mg, 0.106 mmol), palladium(ii) acetate (12 mg, 0.053 mmol), XANTPIIOS (12 mg, 0.021 nmmol), DPPF (12 mg, 0.022 mmol) and cesium carbonate (90 mg, 0.275 mmol) in Dioxane (1.5 mL) was evacuated and back filled with nitrogen three time and was heated at 80° C. for 3 h. LC-MS showed reaction was complete. The reaction mixture was filtered through a pad of Celite, rinsed with EtOAc and the filtrate was concentrated and purification via flash chromatography (0-70% EtOAc in Hexane, 24 g) gave 2-((2-chloro-5-cyano-3-(4-methyl-2-oxopiperazin-1-yl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (60 mg) as a light oil.

Workup

  1. customwas evacuated
  2. additionback filled with nitrogen three time
  3. customreaction
  4. filtrationThe reaction mixture was filtered through a pad of Celite
  5. washrinsed with EtOAc
  6. concentrationthe filtrate was concentrated
  7. custompurification via flash chromatography (0-70% EtOAc in Hexane, 24 g)

Sources & evidence

ORD record
ord-3c524a5e4e2a497ca5f2f766cd85c278
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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