Cesium carbonate → HCID 86686020, compound

HRID 2277726Notes

Reaction equation

HRID 2277726 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH:10]([C:14]2[CH:19]=[N:18][CH:17]=[C:16](Cl)[N:15]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:21][C:22]1[CH:23]=[C:24]2[C:28](=[CH:29][CH:30]=1)[C:27](=[O:31])[NH:26][C:25]2([CH3:33])[CH3:32].[C@H]1(N)CCCC[C@@H]1N.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.[Cu]I.O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH:10]([C:14]2[CH:19]=[N:18][CH:17]=[C:16]([N:26]3[C:27](=[O:31])[C:28]4[C:24](=[CH:23][C:22]([Cl:21])=[CH:30][CH:29]=4)[C:25]3([CH3:33])[CH3:32])[N:15]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 4793071,2-Diaminocyclohexane, (+)-HCID 534152801440520-38-6HCID 71743949HCID 71743949, compound

Product 1

HCID 86686020HCID 86686020, compoundYield 33%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 3-(6-chloro-pyrazin-2-yl)-piperidine-1-carboxylic acid tert-butyl ester (892.5 mg, 3.0 mmol), 5-chloro-3,3-dimethyl-2,3-dihydro-isoindol-1-one (intermediate A-12, 586.5 mg, 3.0 mmol), CuI (171.4 mg, 0.9 mmol), (1S,2S) -cyclohexane-1,2-diamine (205.2 mg, 1.8 mmol) and Cs2CO3 (1.956 g, 6.0 mmol) were dissolved in dioxane (15 mL). The reaction mixture was subjected to microwave reaction at 150° C. for 2.5 hours before it was poured into H2O (50 mL) and extracted with EtOAc (50 mL×2). The combined organic layers were washed with brine, dried over anhy. Na2SO4, filtered and concentrated in vacuo to give a crude product which was then purified by flash chromatography to afford the title compound (450 mg, 33%) as a white solid. MS: 457.2 (M+H+).

Workup

  1. customreaction at 150° C. for 2.5 hours before it
  2. extractionextracted with EtOAc (50 mL×2)
  3. washThe combined organic layers were washed with brine
  4. customdried over anhy
  5. filtrationNa2SO4, filtered
  6. concentrationconcentrated in vacuo
  7. customto give a crude product which
  8. customwas then purified by flash chromatography

Sources & evidence

ORD record
ord-0157333e675b4cd8b7a93c53935e564c
Source dataset
uspto-grants-2015_09
Patent number
US09133158B2

Reaction notes

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