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

HRID 921864Notes

Reaction equation

HRID 921864 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]([NH:36][CH2:37][CH2:38][OH:39])[C:34]=1[Cl:35])[C:30]#[N:31].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.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]([NH:36][CH2:37][CH2:38][OH:39])=[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[CH2:19][CH2:20]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

8

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 867084772-Chloro-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrileHCID 899228303-Amino-4-chloro-5-((2-hydroxyethyl)amino)benzonitrile

Product 1

HCID 899229102-((2-Chloro-5-cyano-3-((2-hydroxyethyl)amino)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrileYield 34.6%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
60 °C

Procedure

A mixture of 2-chloro-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (126 mg, 0.354 mmol), 3-amino-4-chloro-5-((2-hydroxyethyl)amino)benzonitrile (75 mg, 0.354 mmol), palladium(II) acetate (21.08 mg, 0.094 mmol), XANTPHOS (20.50 mg, 0.035 mmol), DPPF (19.65 mg, 0.035 mmol) and cesium carbonate (300 mg, 0.921 mmol) in Dioxane (3 mL) was evacuated and back filled with nitrogen three time and was heated at 60° C. for 1 h. The reaction mixture was filtered through a pad of Celite, rinsed with EtOAc and the filtrate was concentrated. Purification via flash chromatography (0-70% EtOAc in Hexane, 24 g) gave 2-((2-chloro-5-cyano-3-((2-hydroxyethyl)amino)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (65 mg) as a light yellow foam.

Workup

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

Sources & evidence

ORD record
ord-a415414d93dd4c1c9ae462102e99507d
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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