Cesium carbonate → HCID 178419414, compound

HRID 525280Notes

Reaction equation

[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([N:6]=[CH:7][CH:8]=[N:9]2)=[C:4]([O:12][Si](C(C)(C)C)(C)C)[CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CS(O[C@H:31]1[CH2:36][CH2:35][C@H:34]([NH:37][C:38]2[N:43]=[CH:42][C:41](Br)=[CH:40][N:39]=2)[CH2:33][CH2:32]1)(=O)=O>CN1C(=O)CCC1.CCOC(C)=O>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([N:6]=[CH:7][CH:8]=[N:9]2)=[C:4]([O:12][C@@H:31]2[CH2:36][CH2:35][C@H:34]([NH:37][C:38]3[N:39]=[CH:40][CH:41]=[CH:42][N:43]=3)[CH2:33][CH2:32]2)[CH:3]=1

Participants

Conditions

Temperature: 90 °C

Procedure

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).

Workup

additionwas added
washwashed with H2O
dry with materialdried over Na2SO4
concentrationconcentrated
custompurified by medium pressure silica gel chromatography (0-5% MeOH/DCM)

Sources & evidence

ORD record: ord-0f617d3b661f4e79823fbcd390d11188
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09340557B2

Reaction notes

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