4-(3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)morpholine → 1-(2-Chloro-3,6-difluorobenzyl)-7-[3-(morpholin-4-yl)phenyl]-1,2,3,4-tetrahydropyrazino[2,3-b]pyrazine

HRID 80539

Reaktionsgleichung

Reaktionsgleichung von HRID 80539
Br[C:2]1[N:7]=[C:6]2[N:8]([CH2:12][C:13]3[C:18]([F:19])=[CH:17][CH:16]=[C:15]([F:20])[C:14]=3[Cl:21])[CH2:9][CH2:10][NH:11][C:5]2=[N:4][CH:3]=1.[O:22]1[CH2:27][CH2:26][N:25]([C:28]2[CH:29]=[C:30](B3OC(C)(C)C(C)(C)O3)[CH:31]=[CH:32][CH:33]=2)[CH2:24][CH2:23]1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:21][C:14]1[C:15]([F:20])=[CH:16][CH:17]=[C:18]([F:19])[C:13]=1[CH2:12][N:8]1[C:6]2=[N:7][C:2]([C:32]3[CH:31]=[CH:30][CH:29]=[C:28]([N:25]4[CH2:24][CH2:23][O:22][CH2:27][CH2:26]4)[CH:33]=3)=[CH:3][N:4]=[C:5]2[NH:11][CH2:10][CH2:9]1

Komponenten

4

Edukt 2

HCID 41926634-(3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)morpholineHCID 866594227-Bromo-1-(2-chloro-3,6-difluorobenzyl)-1,2,3,4-tetrahydropyrazino[2,3-b]pyrazine

Produkt 1

HCID 461898631-(2-Chloro-3,6-difluorobenzyl)-7-[3-(morpholin-4-yl)phenyl]-1,2,3,4-tetrahydropyrazino[2,3-b]pyrazineAusbeute 61 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 178418397HCID 178418397, VerbindungKatalysator

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

A mixture of 7-bromo-1-(2-chloro-3,6-difluorobenzyl)-1,2,3,4-tetrahydropyrazino[2,3-b]pyrazine (0.14 mmol, 51 mg), 3-morpholinophenylboronic acid pinacol ester (0.16 mmol, 46 mg), and Pd(PPh3)4 (0.015 mmol, 17 mg) was placed in a Schlenk tube. This tube was degassed via 3 cycles of vacuum—refill with N2. THF (3 mL, from sureseal bottle) and aqueous K2CO3 (2.0 M, 1 mL, degassed by bubbling with N2 for 10 min) was then added to the solid mixture in the Schlenk tube. The reaction was stopped after heating at 90° C. for 16 hrs. Extraction and concentration of combined organic layers gave a residue, which was purified on a silica gel column by using 6:1 ratio of CH2Cl2/MeOH (pre-saturated with ammonia gas) as eluents, furnishing 1-(2-chloro-3,6-difluorobenzyl)-7-[3-(morpholin-4-yl)phenyl]-1,2,3,4-tetrahydropyrazino[2,3-b]pyrazine in 61% yield (38 mg).

Aufarbeitung

  1. customwas placed in a Schlenk tube
  2. customThis tube was degassed via 3 cycles of vacuum—refill with N2
  3. additionTHF (3 mL, from sureseal bottle) and aqueous K2CO3 (2.0 M, 1 mL, degassed by bubbling with N2 for 10 min) was then added to the solid mixture in the Schlenk tube
  4. extractionExtraction and concentration of combined organic layers
  5. customgave a residue, which
  6. customwas purified on a silica gel column

Quellen und Nachweise

ORD-Eintrag
ord-a34b11bd5d294f2dbcbaebfa19d2f8f6
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08846664B2

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