Oxalic Acid → HCID 67624953, Verbindung

HRID 1457552Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1457552
[N:1]1[N:2]=[CH:3][N:4]([C:6]2[CH:7]=[C:8]3[C:12](=[CH:13][CH:14]=2)[NH:11][CH:10]=[C:9]3[CH2:15][CH2:16][CH2:17]O)[CH:5]=1.CS(Cl)(=O)=O.[CH2:24]([N:31]1[CH2:36][CH2:35][NH:34][CH2:33][CH:32]1[CH2:37][N:38]([CH3:40])[CH3:39])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.[C:41]([OH:46])(=[O:45])[C:42]([OH:44])=[O:43]>C1COCC1.CN(C=O)C.C(OCC)(=O)C.C(N(CC)CC)C>[C:41]([OH:46])(=[O:45])[C:42]([OH:44])=[O:43].[CH2:24]([N:31]1[CH2:36][CH2:35][N:34]([CH2:17][CH2:16][CH2:15][C:9]2[C:8]3[C:12](=[CH:13][CH:14]=[C:6]([N:4]4[CH:3]=[N:2][N:1]=[CH:5]4)[CH:7]=3)[NH:11][CH:10]=2)[CH2:33][CH:32]1[CH2:37][N:38]([CH3:40])[CH3:39])[C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1

Komponenten

9

Edukt 4

HCID 971Oxalic AcidHCID 31297Methanesulfonyl chlorideHCID 106339143-[5-(1,2,4-triazol-4-yl)-1H-indol-3-yl]propan-1-olHCID 53694502N,N-Dimethyl-1-(phenylmethyl)-2-piperazinemethanamine

Produkt 1

HCID 67624953HCID 67624953, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 6228DimethylformamideLösungsmittelHCID 8028TetrahydrofuranLösungsmittelHCID 8471TriethylamineLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
25 °C

Versuchsvorschrift

To a solution of 3-[5-(1,2,4-triazol-4-yl)-1H-indol-3-yl]propan-1-ol (0.490 g, 2.02 mmol) in THF (100 mL) was added triethylamine (0.62 ml), 6.0 mmol) followed by methanesulphonyl chloride (0.35 mL, 3.03 mmol) and the mixture stirred at 25° C. for 1.5 h. The reaction mixture was filtered and the solvent evaporated. The residue was dissolved in DMF (50 mL) and potassium carbonate (0.35 g) added followed by a solution of 1-benzyl-2-(N,N-dimethylaminomethyl)piperazine (step 2) (0.52 g, 2.22 mmol) in DMF (20 mL). The reaction was heated at 85° C. under N2 for 4 days. The solvent was then removed in vacuo and the residue taken up in ethyl acetate (50 mL) and washed with H2O (3×20 mL). The organic layer was dried (MgSO4) and evaporated. The residue was chromatographed on silica eluting with CH2Cl2 →6% MeOH-1% NH3 --CH2Cl2 to obtain a pale yellow oil that was treated with a solution of oxalic acid in ethyl acetate to obtain a white solid that was filtered and dried to obtain 4-benzyl-3-(N,N-dimethylaminomethyl)-1-[3-(5-(1,2,4-triazol-4-yl) -1H-indol-3-yl)propyl]piperazine oxalate, 105 mg. 1H nmr (free base, 250 MHz, CDCl3) δ 1.92 (2H, m), 2.05-2.9 (13H, m), 2.21 (6H, s), 3.22 (1H, d), 4.20 (1H, d), 7.12 (2H, m), 7.23-7.31 (5H, m), 7.46 (1H, d, J=4 Hz), 7.55 (1H, d, J=1 Hz), 8.38 (1H, br s), 8.46 (2H, s). MS (m/z) 458 (M+1).

Aufarbeitung

  1. filtrationThe reaction mixture was filtered
  2. customthe solvent evaporated
  3. dissolutionThe residue was dissolved in DMF (50 mL)
  4. additionpotassium carbonate (0.35 g) added
  5. temperatureThe reaction was heated at 85° C. under N2 for 4 days
  6. customThe solvent was then removed in vacuo
  7. washwashed with H2O (3×20 mL)
  8. dry with materialThe organic layer was dried (MgSO4)
  9. customevaporated
  10. customThe residue was chromatographed on silica eluting with CH2Cl2 →6% MeOH-1% NH3
  11. customCH2Cl2 to obtain a pale yellow oil that
  12. customto obtain a white solid
  13. filtrationthat was filtered
  14. customdried

Quellen und Nachweise

ORD-Eintrag
ord-8f713c221b2c41b3bfe653c01246a316
Quelldatensatz
uspto-grants-1998_12
Patentnummer
US05849746

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