1,8-Diazabicyclo(5.4.0)undec-7-ene → HCID 57786049、化合物

HRID 1399343ノート

反応式

HRID 1399343 の反応式
[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

参加物

7

反応物 4

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

生成物 1

HCID 57786049HCID 57786049、化合物収率 39%

試薬・触媒・溶媒 2

HCID 1140Toluene溶媒HCID 8857Ethyl Acetate溶媒2 回

実験手順

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%).

後処理

  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

出典と根拠

ORDレコード
ord-ed9201f27e3d4df7b0f7ef189ce7029a
出典データセット
uspto-grants-2014_12
特許番号
US08901141B2

反応ノート

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