1,8-Diazabicyclo(5.4.0)undec-7-ene → HCID 57786049, compound

HRID 1399343Notes

Reaction equation

HRID 1399343 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH:9](O)[C:10]1[N:14]([CH2:15][CH2:16][C:17]([O:19]C)=O)[C:13]2[C:21]([N:25]([CH2:28][CH3:29])[CH2:26][CH3:27])=[CH:22][CH:23]=[CH:24][C:12]=2[N:11]=1.C1(P([N:45]=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1.N12CCCN=C1CCCCC2.Cl.C(N=C=NCCCN(C)C)C>C1(C)C=CC=CC=1.C(OCC)(=O)C>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH:9]1[C:10]2=[N:11][C:12]3[CH:24]=[CH:23][CH:22]=[C:21]([N:25]([CH2:28][CH3:29])[CH2:26][CH3:27])[C:13]=3[N:14]2[CH2:15][CH2:16][C:17](=[O:19])[NH:45]1

Participants

7

Reactant 4

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 199401P,P-Diphenylphosphinic azideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride2×HCID 68772648HCID 68772648, compound

Product 1

HCID 57786049HCID 57786049, compoundYield 39%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a stirred solution of methyl 3-{2-[(2,4-dichlorophenyl)(hydroxy)methyl]-7-(diethylamino)-1H-benzimidazol-1-yl}propanoate (1.00 g, 2.15 mmol) and diphenylphosphoryl azide (1.39 mL, 6.46 mmol) in toluene (11 mL) was added 1,8-diazabicyclo[5.4.0]undec-7-ene (966 μL, 6.46 mol) at room temperature. After 12 h, the reaction mixture was diluted with ethyl acetate, washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by column chromatography on silica gel eluting with a 0-35% ethyl acetate/n-hexane gradient mixture. A solution of the obtained compound was stirred in the presence of 1.9% palladium on fibroin (200 mg) under hydrogen atmosphere at room temperature for 17 h. The catalyst was removed and the filtrate was concentrated in vacuo. The residue was dissolved in tetrahydrofuran (10 mL) and aqueous sodium hydroxide (8 M, 0.5 mL) was added at room temperature. After 15 h, the reaction mixture was concentrated in vacuo. The residue was dissolved in N,N-dimethylformamide (10 mL) and 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (973 mg, 5.08 mmol) was added at room temperature. After 6 h, 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (155 mg, 1.02 mmol) was added. After 2 h, the reaction mixture was diluted with ethyl acetate, washed with water and brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by column chromatography on silica gel eluting with a 0-35% ethyl acetate/n-hexane gradient mixture to afford the desired product as pale yellow solid (334 mg, 0.801 mmol, 39%).

Workup

  1. washwashed with brine
  2. dry with materialdried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by column chromatography on silica gel eluting with a 0-35% ethyl acetate/n-hexane gradient mixture
  6. customThe catalyst was removed
  7. concentrationthe filtrate was concentrated in vacuo
  8. dissolutionThe residue was dissolved in tetrahydrofuran (10 mL)
  9. additionaqueous sodium hydroxide (8 M, 0.5 mL) was added at room temperature
  10. waitAfter 15 h
  11. concentrationthe reaction mixture was concentrated in vacuo
  12. dissolutionThe residue was dissolved in N,N-dimethylformamide (10 mL)
  13. waitAfter 6 h
  14. waitAfter 2 h
  15. washwashed with water and brine
  16. dry with materialdried over sodium sulfate
  17. filtrationfiltered
  18. concentrationconcentrated in vacuo
  19. customThe residue was purified by column chromatography on silica gel eluting with a 0-35% ethyl acetate/n-hexane gradient mixture

Sources & evidence

ORD record
ord-ed9201f27e3d4df7b0f7ef189ce7029a
Source dataset
uspto-grants-2014_12
Patent number
US08901141B2

Reaction notes

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