Reaktion #612462

Reaktionsgleichung

compound 1014

trans-4-((5-bromopyrimidin-2-yl)amino)cyclohexyl methanesulfonate

7-bromoquinoxalin-5-ol

7-bromo-5-((tert-butyldimethylsilyl)oxy)quinoxaline

compound 1018

7-bromo-5-((tert-butyldimethylsilyl)oxy)quinoxaline

cesium carbonate

(trans)-4-(pyrimidin-2-ylamino)cyclohexyl methanesulfonate

trans-4-((5-bromopyrimidin-2-yl)amino)cyclohexyl methanesulfonate

compound 1014

trans-4-((5-bromopyrimidin-2-yl)amino)cyclohexyl methanesulfonate

→

compound 1025

N-((cis)-4-((7-bromoquinoxalin-5-yl)oxy)cyclohexyl)pyrimidin-2-amine

Lösungsmittel

NMP

EtOAc

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONwas added
2. 2
   Waschenwashed with H2O
3. 3
   Trocknendried over Na2SO4
4. 4
   Einengenconcentrated
5. 5
   Sonstigepurified by medium pressure silica gel chromatography (0-5% MeOH/DCM)

Vorschrift

As shown in step 8-i of Scheme 8, to a mixture of 7-bromoquinoxalin-5-ol (compound 1018, 200 mg, 0.89 mmol) and cesium carbonate (579 mg, 1.78 mmol) in NMP (4.0 mL) was added (trans)-4-(pyrimidin-2-ylamino)cyclohexyl methanesulfonate (compound 1014, 241.1 mg, 0.8887 mmol). The mixture was stirred for 18 hours at 90° C., at which time an additional 0.5 eq of compound 1014 (241 mg, 0.89 mmol) was added. After stirring at 90° C. for an additional 6 hours, the reaction mixture was diluted with EtOAc, washed with H2O, dried over Na2SO4, concentrated, and purified by medium pressure silica gel chromatography (0-5% MeOH/DCM) to provide N-((cis)-4-((7-bromoquinoxalin-5-yl)oxy)cyclohexyl)pyrimidin-2-amine (compound 1025): 1H-NMR (300 MHz, CDCl3) δ 9.01-8.77 (m, 2H), 8.29 (d, J=4.8 Hz, 2H), 7.89 (d, J=1.9 Hz, 1H), 7.25 (d, J=2.0 Hz, 1H), 6.53 (t, J=4.8 Hz, 1H), 5.43-5.22 (m, 1H), 4.79 (td, J=5.2, 2.5 Hz, 1H), 4.18-3.95 (m, 1H), 3.51 (s, 1H), 2.22 (td, J=10.2, 9.6, 5.4 Hz, 2H), 2.09-1.86 (m, 6H).

Quelle