7-Morpholinoquinoxalin-5-ol → HCID 178419459, compound

HRID 2200773Notes

Reaction equation

HRID 2200773 reaction equation
[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[CH:8]=[C:9]([OH:17])[C:10]3[N:11]=[CH:12][CH:13]=[N:14][C:15]=3[CH:16]=2)[CH2:3][CH2:2]1.CS(O[C@H:23]1[CH2:28][CH2:27][C@H:26]([NH:29][C:30]2[N:35]=[CH:34][C:33]([Br:36])=[CH:32][N:31]=2)[CH2:25][CH2:24]1)(=O)=O>O1CCOCC1.CCOC(C)=O>[Br:36][C:33]1[CH:34]=[N:35][C:30]([NH:29][C@H:26]2[CH2:27][CH2:28][C@@H:23]([O:17][C:9]3[CH:8]=[C:7]([N:4]4[CH2:5][CH2:6][O:1][CH2:2][CH2:3]4)[CH:16]=[C:15]4[C:10]=3[N:11]=[CH:12][CH:13]=[N:14]4)[CH2:24][CH2:25]2)=[N:31][CH:32]=1

Participants

5

Reactant 2

HCID 1366295107-Morpholinoquinoxalin-5-olHCID 178505326HCID 178505326, compound2×

Product 1

HCID 178419459HCID 178419459, compoundYield 52.5%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

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).

Workup

  1. temperatureAfter cooling
  2. filtrationfiltered through diatomaceous earth
  3. concentrationconcentrated under reduced pressure
  4. custompurified by medium pressure silica gel chromatography (0 to 5% MeOH/DCM gradient)

Sources & evidence

ORD record
ord-d0000274b13a4d6aa7c1caf23bd1f5f5
Source dataset
uspto-grants-2016_06
Patent number
US09359380B2

Reaction notes

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