Cesium carbonate → HCID 86708688, Verbindung

HRID 1430971Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1430971
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[C:28]([Cl:48])=[C:29]([CH:43]=[C:44]([C:46]#[N:47])[CH:45]=1)[O:30][CH:31]1[CH2:35][CH2:34][N:33]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:32]1.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:48][C:28]1[C:27]([NH:26][C:2]2[N:7]=[C:6]([N:8]([CH:18]3[CH2:20][CH2:19]3)[CH2:9][C:10]3[CH:11]=[CH:12][C:13]([O:16][CH3:17])=[CH:14][CH:15]=3)[C:5]3=[N:21][CH:22]=[C:23]([C:24]#[N:25])[N:4]3[N:3]=2)=[CH:45][C:44]([C:46]#[N:47])=[CH:43][C:29]=1[O:30][CH:31]1[CH2:35][CH2:34][N:33]([C:36]([O:38][C:39]([CH3:42])([CH3:40])[CH3:41])=[O:37])[CH2:32]1

Komponenten

8

Edukt 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-carbonitrile2×HCID 86708687HCID 86708687, Verbindung

Produkt 1

HCID 86708688HCID 86708688, VerbindungAusbeute 64,9 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)KatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

A mixture of 2-chloro-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (Intermediate 9)(50 mg, 0.141 mmol), (+/−)-tert-butyl 3-(3-amino-2-chloro-5-cyanophenoxy)pyrrolidine-1-carboxylate (47.6 mg, 0.141 mmol), palladium(II) acetate (8.38 mg, 0.037 mmol), xantphos (8.15 mg, 0.014 mmol), DPPF (7.81 mg, 0.014 mmol) and cesium carbonate (119 mg, 0.366 mmol) in dioxane (1 ml) was evacuated and back filled with nitrogen three time and was heated at 70° C. for 3 h. The reaction mixture was filtered through a pad of celite, the filtrate was concentrated, the crude product was purified by flash chromatography on silica gel using an automated ISCO system (40 g gold column, eluting with 0-40% ethyl acetate/dichloromethane). (+/−)-tert-butyl 3-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenoxy)pyrrolidine-1-carboxylate (60 mg) was obtained as a colorless oil which was carried as such to the next reaction.

Aufarbeitung

  1. customwas evacuated
  2. additionback filled with nitrogen three time
  3. filtrationThe reaction mixture was filtered through a pad of celite
  4. concentrationthe filtrate was concentrated
  5. customthe crude product was purified by flash chromatography on silica gel using
  6. washan automated ISCO system (40 g gold column, eluting with 0-40% ethyl acetate/dichloromethane)

Quellen und Nachweise

ORD-Eintrag
ord-3b7958a19342467485c10ba9659c9552
Quelldatensatz
uspto-grants-2015_01
Patentnummer
US08940736B2

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