1,2-Dichloroethane → HCID 178497906, compound

HRID 1992801Notes

Reaction equation

HRID 1992801 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:13]=[C:12]([C:14](O)=[O:15])[N:11]([CH2:17][C:18]3[CH:23]=[CH:22][C:21]([C:24]([O:26][CH3:27])=[O:25])=[CH:20][N:19]=3)[N:10]=2)[CH:5]=[CH:6][C:7]=1[Cl:8].[CH:28]1[CH:33]=N[C:31]2[N:34](O)N=N[C:30]=2[CH:29]=1.[C:38](NC1CCCCC1)([CH3:41])([CH3:40])[CH3:39].[CH3:49]CN(C(C)C)C(C)C.C(Cl)CCl>CN(C=O)C.C(OCC)(=O)C>[C:38]([C@@H:28]1[CH2:29][CH2:30][C@H:31]([NH:34][C:14]([C:12]2[N:11]([CH2:17][C:18]3[CH:23]=[CH:22][C:21]([C:24]([O:26][CH3:27])=[O:25])=[CH:20][N:19]=3)[N:10]=[C:9]([C:4]3[CH:5]=[CH:6][C:7]([Cl:8])=[C:2]([Cl:1])[CH:3]=3)[CH:13]=2)=[O:15])[CH2:49][CH2:33]1)([CH3:41])([CH3:40])[CH3:39]

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 103920N-tert-ButylcyclohexylamineHCID 181649HOAtHCID 68426417HCID 68426417, compound

Product 1

HCID 178497906HCID 178497906, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of the intermediate from step F (464 mg, 0.90 mmol) in DMF (10 mL) was added HOAt (244 mg, 1.79 mmol), tert-butyl-cyclohexylamine (426 μL, 2.39 mmol), DIEA (623 μL, 3.57 mmol) and EDC (343 mg, 1.79 mmol). The resulting slurry was left stirring at room temperature overnight. The reaction was stirred to 50° C. for 3 hours. It was cooled to room temperature, diluted with ethyl acetate, washed with 1N HCl, saturated NaHCO3 solution, and dried over anhydrous Na2SO4. The solution was filtered and concentrated in vacuo. The residue was purified by flash chromatography using 30% ethyl acetate-hexanes. The trans and cis isomers were obtained in a 2:1 ratio. Isomer A (trans isomer): 1H NMR (CDCl3, 500 MHz): 9.16 (d, J=1.8 Hz, 1H), 8.31 (dd, J=2.1, 8.3 Hz, 1H), 7.89 (d, J=1.9 Hz, 1H), 7.61 (dd, J=2.1, 8.5 Hz, 1H), 7.46 (d, J=8.5 Hz, 1H), 7.27 (d, J=8.2 Hz, 1H), 7.24 (d, J=7.8 Hz, 1H), 6.92 (s, 1H), 5.89 (s, 2H), 3.97 (s, 3H), 3.9 (m, 1H), 2.14 (bd, J=11.3 Hz, 2H), 1.87 (bd, J=12.6 Hz, 2H), 1.0-1.4 (m, 5H), 0.88 (s, 9H). LC-MS: 2.81 min; (M+H)=529.2. Isomer B (cis isomer): 1H NMR (CDCl3, 500 MHz): 9.18 (d, J=2.1 Hz, 1H), 8.33 (dd, J=2.0, 8.2 Hz, 1H), 7.92 (d, J=2.0 Hz, 1H), 7.64 (dd, J=2.1, 8.3 Hz, 1H), 7.48 (d, J=8.2 Hz, 1H), 7.34 (d, J=8.0 Hz, 1H), 6.9 (s, 1H), 5.88 (s, 2H), 4.3 (m, 1H), 3.97 (s, 3H), 2.01 (d, J=13.8 Hz, 2H), 1.73 (m, 2H), 1.65 (m, 2H), 1.29 (m, 2H), 0.89 (s, 9H). LC-MS: 2.81 min; (M+H)=529.2.

Workup

  1. waitThe resulting slurry was left
  2. stirringThe reaction was stirred to 50° C. for 3 hours
  3. temperatureIt was cooled to room temperature
  4. washwashed with 1N HCl, saturated NaHCO3 solution
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationThe solution was filtered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash chromatography
  9. customThe trans and cis isomers were obtained in a 2:1 ratio
  10. custom2.81 min
  11. custom2.81 min

Sources & evidence

ORD record
ord-45454c627e2f4bd2bfb8c60e448abc6c
Source dataset
uspto-grants-2010_01
Patent number
US07649009B2

Reaction notes

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