Reaktion #2287955

Reaktionsgleichung

7-morpholinoquinoxalin-5-ol

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

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

compound 1014

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

→

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

Ausbeute 52.5%

Lösungsmittel

EtOAc

dioxane

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturAfter cooling
2. 2
   Filtrationfiltered through diatomaceous earth
3. 3
   Einengenconcentrated under reduced pressure
4. 4
   Sonstigepurified by medium pressure silica gel chromatography (0 to 5% MeOH/DCM gradient)

Vorschrift

As shown in step 6-viii of Scheme 6, a solution of 7-morpholinoquinoxalin-5-ol (100 mg, 0.432 mmol), (trans)-4-((5-bromopyrimidin-2-yl)amino)cyclohexyl methanesulfonate (compound 1014, 303 mg, 0.865 mmol), and CsCO3 (282 mg, 0.865 mmol) in dioxane (1.0 mL was stirred for 16 hours at 105° C. After cooling, the reaction mixture was diluted with EtOAc, filtered through diatomaceous earth, concentrated under reduced pressure, and purified by medium pressure silica gel chromatography (0 to 5% MeOH/DCM gradient) to produce 5-bromo-N-((cis)-4-((7-morpholinoquinoxalin-5-yl)oxy)cyclohexyl)pyrimidin-2-amine (compound 1020, 110 mg) as a yellow foam: 1H-NMR (400 MHz, CDCl3) δ 8.70 (d, J=2.0 Hz, 1H), 8.64 (d, J=1.9 Hz, 1H), 8.29 (s, 2H), 6.98 (d, J=2.5 Hz, 1H), 6.92 (d, J=2.5 Hz, 1H), 5.29 (d, J=8.3 Hz, 1H), 4.81 (s, 1H), 4.04-3.84 (m, 4H), 3.42-3.31 (m, 4H), 2.22 (s, 2H), 1.92 (d, J=4.9 Hz, 6H).

Quelle