Hydrochloric Acid → HCID 67387585, Verbindung

HRID 401901Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 401901
[ClH:1].Cl.[CH2:3]([C:7]1[N:8]=[N:9][C:10]([O:26][CH:27]2[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]2)=[CH:11][C:12]=1[C:13]1[CH:18]=[CH:17][C:16]([O:19][CH:20]2[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]2)=[CH:15][CH:14]=1)[CH2:4][CH2:5][CH3:6].Br[CH2:34][CH2:35][CH:36]1[O:41][CH2:40][CH2:39][CH2:38][O:37]1.C(=O)([O-])[O-].[K+].[K+].Cl>CN(C=O)C.O.CCOC(C)=O.C(Cl)Cl.CCOCC>[ClH:1].[ClH:1].[CH2:3]([C:7]1[N:8]=[N:9][C:10]([O:26][CH:27]2[CH2:32][CH2:31][N:30]([CH2:34][CH2:35][CH:36]3[O:41][CH2:40][CH2:39][CH2:38][O:37]3)[CH2:29][CH2:28]2)=[CH:11][C:12]=1[C:13]1[CH:14]=[CH:15][C:16]([O:19][CH:20]2[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]2)=[CH:17][CH:18]=1)[CH2:4][CH2:5][CH3:6]

Komponenten

9

Edukt 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 5206561,3-Dioxane, 2-(2-bromoethyl)-HCID 67375293HCID 67375293, Verbindung

Produkt 1

HCID 67387585HCID 67387585, VerbindungAusbeute 73,7 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 3283Diethyl EtherLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 22728543Water ethylacetateLösungsmittel

Versuchsvorschrift

To a solution of 3-butyl-4-(4-cyclohexyloxy-phenyl)-6-(piperidin-4-yloxy)-pyridazine dihydrochloride (Example 14, 0.1 mmol, 49 mg) in DMF (1 mL) was added 2-(2-bromoethyl)-1,3-dioxane (0.3 mmol, 40 μL), and potassium carbonate (0.4 mmol, 56 mg). The mixture was stirred at room temperature for 3 hours. It was then diluted with water/EtOAc. The organic layers were combined, dried, and condensed in vacuo and the residue was purified by silica gel chromatography (DCM to DCM+10% 2N ammonia in MeOH) to give a colorless sticky solid, which was dissolved in DCM (1 mL), 1N HCl in ether (1 mL) was added, kept at room temperature for 10 min, condensed, triturated with hexanes to provide the title compound (22 mg). LCMS: m/z 525 [M+1]. 1H NMR (400 MHz, CD3OD): δ 7.72 and 7.81 (1H, s), 7.44-7.49 (2H, m), 7.12-7.17 (2H, m), 5.38-5.57 (1H, m), 4.76-4.79 (1H, m), 4.41-4.48 (1H, m), 4.06-4.13 (2H, m), 3.72-3.86 (3H, m), 3.55-3.60 (1H, m), 3.22-3.39 (4H, m), 3.12-3.17 (2H, m), 2.23-2.57 (3H, m), 1.98-2.17 (6H, m), 1.79-1.86 (2H, m), 1.23-1.64 (11H, m), 0.82 (3H, t).

Aufarbeitung

  1. customdried
  2. customcondensed in vacuo
  3. customthe residue was purified by silica gel chromatography (DCM to DCM+10% 2N ammonia in MeOH)
  4. customto give a colorless sticky solid, which
  5. waitkept at room temperature for 10 min
  6. customcondensed
  7. customtriturated with hexanes

Quellen und Nachweise

ORD-Eintrag
ord-c364149d75914cc98929208abc9054ca
Quelldatensatz
uspto-grants-2014_06
Patentnummer
US08741900B2

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