Cesium carbonate → (+/-) Tert-butyl(2-((2-chloro-5-cyano-3-(3-(morpholine-4-carbonyl)-4-(oxetan-3-yl)piperazin-1-yl)phenyl)amino)-7-cyanoimidazo[2,1-f][1,2,4]triazin-4-yl)(cyclopropyl)carbamate

HRID 1430875Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1430875
[CH:1]1([N:4](CC2C=CC(OC)=CC=2)[C:5]2[C:10]3=[N:11][CH:12]=[C:13]([C:14]#[N:15])[N:9]3[N:8]=[C:7](S(C)(=O)=O)[N:6]=2)[CH2:3][CH2:2]1.[NH2:29][C:30]1[CH:31]=[C:32]([CH:35]=[C:36]([N:39]2[CH2:44][CH2:43][N:42]([CH:45]3[CH2:48][O:47][CH2:46]3)[CH:41]([C:49]([N:51]3[CH2:56][CH2:55][O:54][CH2:53][CH2:52]3)=[O:50])[CH2:40]2)[C:37]=1[Cl:38])[C:33]#[N:34].[CH3:57][C:58]1(C)[C:84]2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=C[C:59]1=2.[C:99](=[O:102])([O-])[O-:100].[Cs+].[Cs+]>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].O1CCOCC1>[Cl:38][C:37]1[C:36]([N:39]2[CH2:44][CH2:43][N:42]([CH:45]3[CH2:48][O:47][CH2:46]3)[CH:41]([C:49]([N:51]3[CH2:56][CH2:55][O:54][CH2:53][CH2:52]3)=[O:50])[CH2:40]2)=[CH:35][C:32]([C:33]#[N:34])=[CH:31][C:30]=1[NH:29][C:7]1[N:6]=[C:5]([N:4]([CH:1]2[CH2:3][CH2:2]2)[C:99](=[O:102])[O:100][C:58]([CH3:84])([CH3:59])[CH3:57])[C:10]2=[N:11][CH:12]=[C:13]([C:14]#[N:15])[N:9]2[N:8]=1

Komponenten

8

Edukt 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86708519HCID 86708519, Verbindung2×HCID 867085723-Amino-4-chloro-5-(3-(morpholine-4-carbonyl)-4-(oxetan-3-yl)piperazin-1-yl)benzonitrile

Produkt 1

HCID 86708573(+/-) Tert-butyl(2-((2-chloro-5-cyano-3-(3-(morpholine-4-carbonyl)-4-(oxetan-3-yl)piperazin-1-yl)phenyl)amino)-7-cyanoimidazo[2,1-f][1,2,4]triazin-4-yl)(cyclopropyl)carbamateAusbeute 713,2 %

Reagenzien, Katalysatoren, Lösungsmittel 3

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

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

(+/−) Tert-butyl (2-chloro-7-cyanoimidazo[2,1-f][1,2,4]triazin-4-yl)(cyclopropyl)carbamate (Intermediate 1) (30 mg, 0.090 mmol), 3-amino-4-chloro-5-(3-(morpholine-4-carbonyl)-4-(oxetan-3-yl)piperazin-1-yl)benzonitrile (36.4 mg, 0.090 mmol), palladium (II) acetate (6.04 mg, 0.027 mmol), dppf (4.97 mg, 8.96 pimp, Xantphos (5.19 mg, 8.96 μmol), and cesium carbonate (52.6 mg, 0.161 mmol) were combined in a 10 ml flask and Dioxane (1 mL) was added. The flask was evacuated and backfilled with N2 3×, then heated at 100° C. for 1 h. The reaction was cooled to rt and filtered through celite, rinsing with EtOAc. The solvent was removed in vacuo and the crude material was purified by flash column (0-5% MeOH/DCM). (+/−) Tert-butyl (2-((2-chloro-5-cyano-3-(3-(morpholine-4-carbonyl)-4-(oxetan-3-yl)piperazin-1-yl)phenyl)amino)-7-cyanoimidazo[2,1-f][1,2,4]triazin-4-yl)(cyclopropyl)carbamate (45 mg) was obtained as a yellow glass.

Aufarbeitung

  1. customThe flask was evacuated
  2. temperatureThe reaction was cooled to rt
  3. filtrationfiltered through celite
  4. washrinsing with EtOAc
  5. customThe solvent was removed in vacuo
  6. customthe crude material was purified by flash column (0-5% MeOH/DCM)

Quellen und Nachweise

ORD-Eintrag
ord-08f5c595f4e84f1886b33f0c2e140de1
Quelldatensatz
uspto-grants-2015_01
Patentnummer
US08940736B2

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