Ethylenediamine → HCID 59161290, compound

HRID 545523Notes

Reaction equation

HRID 545523 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:12](=[CH:13][C:14]=1[F:15])[N:11]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=1)[C:10]1[CH2:9][CH2:8][CH:7]([NH:24][C:25](=[O:29])[CH:26]([CH3:28])[CH3:27])[CH2:6][C:5]2=1.BrC1C(F)=C2C(=CC=1)[N:40](CC1C=CC=C(F)C=1)[C:39]1CCC(NC(=O)C(C)C)CC2=1.[Cu]C#N.C(N)CN>CN1CCCC1=O.CCOC(C)=O.O.[Cu]I>[C:39]([C:2]1[CH:3]=[C:4]2[C:12](=[CH:13][C:14]=1[F:15])[N:11]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=1)[C:10]1[CH2:9][CH2:8][CH:7]([NH:24][C:25](=[O:29])[CH:26]([CH3:28])[CH3:27])[CH2:6][C:5]2=1)#[N:40]

Participants

9

Reactant 4

HCID 3301EthylenediamineHCID 59161197HCID 59161197, compoundHCID 59161316HCID 59161316, compoundHCID 178418546HCID 178418546, compound

Product 1

HCID 59161290HCID 59161290, compoundYield 20%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
130 °C

Procedure

Dissolve a 65:35 mixture of N-[6-bromo-7-fluoro-9-(3-fluoro-benzyl)-2,3,4,9-tetrahydro-1H-carbazol-3-yl]-isobutyramide and N-[6-bromo-5-fluoro-9-(3-fluoro-benzyl)-2,3,4,9-tetrahydro-1H-carbazol-3-yl]-isobutyramide (500 mg, 1.08 mmol; Preparation 20) in N-methylpyrrolidinone (10 mL). Sparge the resulting solution with nitrogen for 30 min, then add copper(I) cyanide (291 mg, 3.25 mmol) and copper(I) iodide (619 mg, 3.25 mmol). Heat to 130° C. for three days, then cool to room temperature. Dilute the reaction mixture with EtOAc (200 mL) and water (100 mL). Add ethylene diamine until all the solids are dissolved (about 20 mL). Separate the layers, then wash the organic layer with water (3×75 mL). Dry the organic portion (MgSO4), filter, and concentrate the organic layer to afford 474 mg of crude product. Separate the title compound from this mixture by silica gel chromatography (0-10% EtOAc/CHCl3), affording the title compound as a white solid in 20% yield. MS (ES): m/z 408 (M+1), 406 (M−1); HPLC: Rt=2.51 min, (96%).

Workup

  1. dissolutionDissolve
  2. customSparge the resulting solution with nitrogen for 30 min
  3. temperaturecool to room temperature
  4. customSeparate the layers
  5. washwash the organic layer with water (3×75 mL)
  6. dry with materialDry the organic portion (MgSO4)
  7. filtrationfilter
  8. concentrationconcentrate the organic layer
  9. customto afford 474 mg of crude product
  10. customSeparate the title compound from this mixture by silica gel chromatography (0-10% EtOAc/CHCl3)

Sources & evidence

ORD record
ord-9cdace98fff74fcc8fd02e65d6ce3fc8
Source dataset
uspto-grants-2011_05
Patent number
US07935722B2

Reaction notes

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