Cesium carbonate → HCID 178420802, compound

HRID 525268Notes

Reaction equation

HRID 525268 reaction equation
Br[C:2]1[C:10]2[C:6](=[N:7][O:8][N:9]=2)[CH:5]=[C:4]([N:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)[CH:3]=1.Cl.[N:18]1[CH:23]=[CH:22][CH:21]=[N:20][C:19]=1[NH:24][C@H:25]1[CH2:30][CH2:29][C@@H:28]([NH2:31])[CH2:27][CH2:26]1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[O:14]1[CH2:15][CH2:16][N:11]([C:4]2[CH:3]=[C:2]([NH:31][C@H:28]3[CH2:27][CH2:26][C@@H:25]([NH:24][C:19]4[N:18]=[CH:23][CH:22]=[CH:21][N:20]=4)[CH2:30][CH2:29]3)[C:10]3[C:6]([CH:5]=2)=[N:7][O:8][N:9]=3)[CH2:12][CH2:13]1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 5303318HCID 5303318, compound2×HCID 178479268HCID 178479268, compound

Product 1

HCID 178420802HCID 178420802, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

As shown in step 5-iii of Scheme 5, a mixture of 4-bromo-6-morpholinobenzo[c][1,2,5]oxadiazole (compound 1012, 147 mg, 0.5 mmol), (cis)-N1-(pyrimidin-2-yl)cyclohexane-1,4-diamine hydrochloride (120 mg, 0.6 mmol), (rac)-BINAP (32 mg, 0.05 mmol), Pd2(dba)3 (24 mg, 0.026 mmol), and cesium carbonate (506 mg, 1.55 mmol) in toluene (5 mL) was flushed with nitrogen gas and stirred overnight at 90° C. under an atmosphere of nitrogen. The mixture was filtered though a layer of diatomaceous earth, concentrated under reduced pressure, and purified by medium pressure silica gel chromatography (0 to 80% EtOAc/hexanes gradient) to provide (cis)-N1-(6-morpholinobenzo[c][1,2,5]oxadiazol-4-yl)-N4-(pyrimidin-2-yl)cyclohexane-1,4-diamine (compound 23) as an orange solid: 1H-NMR (300 MHz, CDCl3) δ 8.20 (d, J=4.9 Hz, 2H), 6.46 (t, J=4.8 Hz, 1H), 6.05 (d, J=1.6 Hz, 1H), 5.82 (s, 1H), 5.24 (s, 1H), 4.82 (d, J=7.0 Hz, 1H), 3.98 (s, 1H), 3.85-3.72 (m, 4H), 3.60 (s, 1H), 3.23-3.06 (m, 4H), 1.95-1.62 (m, 8H).

Workup

  1. customwas flushed with nitrogen gas
  2. filtrationThe mixture was filtered though a layer of diatomaceous earth
  3. concentrationconcentrated under reduced pressure
  4. custompurified by medium pressure silica gel chromatography (0 to 80% EtOAc/hexanes gradient)

Sources & evidence

ORD record
ord-cdba3f0feae446e29638993007732ab0
Source dataset
uspto-grants-2016_05
Patent number
US09340557B2

Reaction notes

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