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

HRID 921895Notes

Reaction equation

HRID 921895 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([C:11]([CH3:13])=[CH2:12])[C:9]=1[Cl:10])[C:5]#[N:6].Cl[C:15]1[N:20]=[C:19]([N:21]([CH:31]2[CH2:33][CH2:32]2)[CH2:22][C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=2)[C:18]2=[N:34][CH:35]=[C:36]([C:37]#[N:38])[N:17]2[N:16]=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(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].CC([O-])=O.CC([O-])=O.[Pd+2]>[Cl:10][C:9]1[C:8]([C:11]([CH3:13])=[CH2:12])=[CH:7][C:4]([C:5]#[N:6])=[CH:3][C:2]=1[NH:1][C:15]1[N:20]=[C:19]([N:21]([CH:31]2[CH2:33][CH2:32]2)[CH2:22][C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=2)[C:18]2=[N:34][CH:35]=[C:36]([C:37]#[N:38])[N:17]2[N:16]=1

Participants

7

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 89922572HCID 89922572, compound

Product 1

HCID 1182534612-((2-Chloro-5-cyano-3-(prop-1-en-2-yl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrileYield 76.6%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)Catalyst

Conditions

Temperature
100 °C

Procedure

A mixture of 3-amino-4-chloro-5-(prop-1-en-2-yl)benzonitrile (367 mg, 1.91 mmol), 2-chloro-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (676 mg, 1.91 mmol), Cs2CO3 (1.24 gm, 3.81 mmol), DPPF (106 mg, 0.191 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethyxanthene (110 mg, 0.191 mmol) and Pd(OAc)2 (128 mg, 0.572 mmol) in a microwave vial that was flushed with nitrogen. Dioxane (16 mL) was added and the vial was sealed and heated at 100° C. for 4 hr. The reaction was diluted with EtOAc and filtered through celite. The solvent was removed from the filtrate and radial silica gel chromatography eluting with hexane containing 5 to 40% EtOAc afforded 2-((2-chloro-5-cyano-3-(prop-1-en-2-yl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (748 mg) as a solid.

Workup

  1. customwas flushed with nitrogen
  2. additionDioxane (16 mL) was added
  3. customthe vial was sealed
  4. additionThe reaction was diluted with EtOAc
  5. filtrationfiltered through celite
  6. customThe solvent was removed from the filtrate and radial silica gel chromatography
  7. washeluting with hexane containing 5 to 40% EtOAc

Sources & evidence

ORD record
ord-ab7e2e41b0e0489d8f3860ed071485e2
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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