Cesium carbonate → HCID 86686017, compound

HRID 2277722Notes

Reaction equation

HRID 2277722 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=[O:11])[NH:6][C:5]2([CH3:13])[CH3:12].Br[C:15]1[CH:16]=[C:17]([CH:21]2[CH2:25][CH2:24][N:23]([C:26](=[O:28])[CH3:27])[CH2:22]2)[CH:18]=[N:19][CH:20]=1.[C@H]1(N)CCCC[C@@H]1N.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.[Cu]I.O>[C:26]([N:23]1[CH2:24][CH2:25][CH:21]([C:17]2[CH:16]=[C:15]([N:6]3[C:5]([CH3:13])([CH3:12])[C:4]4[C:8](=[CH:9][CH:10]=[C:2]([Cl:1])[CH:3]=4)[C:7]3=[O:11])[CH:20]=[N:19][CH:18]=2)[CH2:22]1)(=[O:28])[CH3:27]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 4793071,2-Diaminocyclohexane, (+)-HCID 71743949HCID 71743949, compoundHCID 86686016HCID 86686016, compound

Product 1

HCID 86686017HCID 86686017, compoundYield 10%

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 5-chloro-3,3-dimethyl-2,3-dihydro-isoindol-1-one (intermediate A-12, 160 mg, 0.82 mmol), 1-[3-(5-bromo-pyridin-3-yl)-pyrrolidin-1-yl]-ethanone (160 mg, 0.6 mmol), CuI (34 mg, 0.8 mmol), (1S,2S)-cyclohexane-1,2-diamine (41 mg, 0.36 mmol) and Cs2CO3 (390 mg, 1.2 mmol) were dissolved in dioxane (5 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 (25 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 Prep-HPLC to yield the title compound (23 mg, 10%) as a white solid. MS: 384.2 (M+H+).

Workup

  1. customreaction at 150° C. for 2.5 hours before it
  2. extractionextracted with EtOAc (25 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 Prep-HPLC

Sources & evidence

ORD record
ord-93e07cc334b341ad975175909a308831
Source dataset
uspto-grants-2015_09
Patent number
US09133158B2

Reaction notes

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