Cesium carbonate → (2S)-2-((6-(1-methyl-1H-pyrazol-4-yl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-1-yl)methyl)-4-(5-(1-(2-(tetrahydro-2H-pyran-2-yloxy)ethyl)-1H-pyrazol-4-yl)pyrimidin-2-yl)morpholine

HRID 1478569Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1478569
Br[C:2]1[CH:3]=[N:4][C:5]([N:8]2[CH2:13][CH2:12][O:11][C@H:10]([CH2:14][N:15]3[C:19]4=[N:20][C:21]([C:24]5[CH:25]=[N:26][N:27]([CH3:29])[CH:28]=5)=[CH:22][N:23]=[C:18]4[N:17]=[N:16]3)[CH2:9]2)=[N:6][CH:7]=1.[O:30]1[CH2:35][CH2:34][CH2:33][CH2:32][CH:31]1[O:36][CH2:37][CH2:38][N:39]1[CH:43]=[C:42](B2OC(C)(C)C(C)(C)O2)[CH:41]=[N:40]1.C(=O)([O-])[O-].[Cs+].[Cs+]>COCOC.O.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.Cl[Pd]Cl.[Fe+2]>[CH3:29][N:27]1[CH:28]=[C:24]([C:21]2[N:20]=[C:19]3[N:15]([CH2:14][C@H:10]4[O:11][CH2:12][CH2:13][N:8]([C:5]5[N:4]=[CH:3][C:2]([C:42]6[CH:41]=[N:40][N:39]([CH2:38][CH2:37][O:36][CH:31]7[CH2:32][CH2:33][CH2:34][CH2:35][O:30]7)[CH:43]=6)=[CH:7][N:6]=5)[CH2:9]4)[N:16]=[N:17][C:18]3=[N:23][CH:22]=2)[CH:25]=[N:26]1

Komponenten

7

Edukt 3

HCID 10796Cesium carbonateHCID 593418191-[2-(oxan-2-yloxy)ethyl]-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 73507291HCID 73507291, Verbindung

Produkt 1

HCID 118364842(2S)-2-((6-(1-methyl-1H-pyrazol-4-yl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-1-yl)methyl)-4-(5-(1-(2-(tetrahydro-2H-pyran-2-yloxy)ethyl)-1H-pyrazol-4-yl)pyrimidin-2-yl)morpholineAusbeute 77 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 962WaterLösungsmittelHCID 8020DimethoxymethaneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

(S)-4-(5-bromopyrimidin-2-yl)-2-((6-(1-methyl-1H-pyrazol-4-yl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-1-yl)methyl)morpholine 300 mg (0.66 mmol) was dissolved in dimethoxymethane 12 ml, and 1-(2-(tetrahydro-2H-pyran-2-yloxy)ethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane-2-yl)-1H-pyrazole 450 mg (1.39 mmol) was added. Cesium carbonate 641 mg (1.97 mmol) was dissolved in distilled water 3 ml, which was then added to the reaction solution. PdCl2(dppf)2 27 mg (0.03 mmol) was added, and the mixture was purged with N2 (g), followed by stirring at 80° C. for 4 hours. After the completion of the reaction, the reaction mixture was extracted with ethyl acetate and brine, and the organic layer was dried over Na2SO4. Prep LC with 5% MeOH/MC gave a product 290 mg (77%).

Aufarbeitung

  1. additionwhich was then added to the reaction solution
  2. customthe mixture was purged with N2 (g)
  3. customAfter the completion of the reaction
  4. extractionthe reaction mixture was extracted with ethyl acetate and brine
  5. dry with materialthe organic layer was dried over Na2SO4

Quellen und Nachweise

ORD-Eintrag
ord-e5b3321557a54708ab93aa6cc25abb6d
Quelldatensatz
uspto-grants-2016_08
Patentnummer
US09403831B2

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