Cesium carbonate → 2-((5-Cyano-2,4-difluorophenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

HRID 921783Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 921783
[NH2:1][C:2]1[C:3]([F:11])=[CH:4][C:5]([F:10])=[C:6]([CH:9]=1)[C:7]#[N:8].Cl[C:13]1[N:18]=[C:17]([N:19]([CH:29]2[CH2:31][CH2:30]2)[CH2:20][C:21]2[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=2)[C:16]2=[N:32][CH:33]=[C:34]([C:35]#[N:36])[N:15]2[N:14]=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]>[C:7]([C:6]1[C:5]([F:10])=[CH:4][C:3]([F:11])=[C:2]([NH:1][C:13]2[N:18]=[C:17]([N:19]([CH:29]3[CH2:31][CH2:30]3)[CH2:20][C:21]3[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=3)[C:16]3=[N:32][CH:33]=[C:34]([C:35]#[N:36])[N:15]3[N:14]=2)[CH:9]=1)#[N:8]

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 668484065-Amino-2,4-difluorobenzonitrileHCID 867084772-Chloro-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile2×

Produkt 1

HCID 867086762-((5-Cyano-2,4-difluorophenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrileAusbeute 86,9 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 167845palladium(II) acetateKatalysatorHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)Katalysator

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A mixture of 5-amino-2,4-difluorobenzonitrile (300 mg, 1.947 mmol), 2-chloro-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (Intermediate 9) (691 mg, 1.947 mmol), Cs2CO3 (1268 mg, 3.89 mmol), DPPF (108 mg, 0.195 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethyxanthene (113 mg, 0.195 mmol), and Pd(OAc)2 (131 mg, 0.584 mmol) in a microwave vial 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 and radial silica gel chromatography eluting with hexane containing 5 to 40% EtOAc afforded 2-((5-cyano-2,4-difluorophenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (799 mg) as a foam.

Aufarbeitung

  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
  7. washradial silica gel chromatography eluting with hexane containing 5 to 40% EtOAc

Quellen und Nachweise

ORD-Eintrag
ord-20476b8e0906465188ca113028db9b26
Quelldatensatz
uspto-grants-2016_03
Patentnummer
US09273057B2

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