Imidazole → HCID 74931512, compound

HRID 1095116Notes

Reaction equation

HRID 1095116 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:32])[C:10]3([CH:15]([C:16]4[CH:21]=[CH:20][CH:19]=[C:18]([Cl:22])[CH:17]=4)[CH2:14][C:13](=[O:23])[NH:12][CH:11]3[C:24]3[CH:29]=[C:28]([Cl:30])[CH:27]=[CH:26][C:25]=3I)[C:5]2=[CH:4][CH:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].C[N:40]([CH3:46])[CH2:41][CH2:42][N:43](C)C.N1C=CN=C1>CN(C)C=O.[Cu]I>[Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:32])[C:10]3([CH:15]([C:16]4[CH:21]=[CH:20][CH:19]=[C:18]([Cl:22])[CH:17]=4)[CH2:14][C:13](=[O:23])[NH:12][CH:11]3[C:24]3[CH:29]=[C:28]([Cl:30])[CH:27]=[CH:26][C:25]=3[N:40]3[CH:41]=[CH:42][N:43]=[CH:46]3)[C:5]2=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 795ImidazoleHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 10796Cesium carbonateHCID 76567899HCID 76567899, compound

Product 1

HCID 74931512HCID 74931512, compoundYield 5.9%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
170 °C

Procedure

A solution of racemic(2′R, 3R, 4′S)-6-chloro-4′-(3-chlorophenyl)-2′-(5-chloro-2-iodophenyl)spiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione (0.3 g, 0.5 mmol) in anhydrous N,N-dimethylformamide (10 mL) was added Cs2CO3 (1.2 g, 4 mmol) (Aldrich), CuI (95 mg, 0.5 mmol) (Aldrich), N,N,N′,N′-tetramethylethylenediamine (0.2 mL, 2 mmol), and imidazole (80 mg, 1 mmol). The mixture was heated under nitrogen at 170° C. for 0.5 h. The mixture was cooled to room temperature, partitioned between ethyl acetate and water. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The organic layers were combined, washed with brine, dried over MgSO4, and concentrated. The residue was purified by chromatography (EtOAc:MeOH=9: 1) to give a crude product 997 mg), which was further purified by RP-HPLC to give racemic(2′R, 3R, 4′S)-6-chloro-2′-(5-chloro-2-imidazol-1-yl-phenyl)-4′-(3-chlorophenyl)spiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione as a white solid (Yield 16 mg).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. custompartitioned between ethyl acetate and water
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with ethyl acetate
  5. washwashed with brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. customThe residue was purified by chromatography (EtOAc:MeOH=9: 1)
  9. customto give a crude product 997 mg), which
  10. customwas further purified by RP-HPLC

Sources & evidence

ORD record
ord-b5ffe64f9b9a4fe192dbc9904fc42943
Source dataset
uspto-grants-2012_03
Patent number
US08134001B2

Reaction notes

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