Dimethylamine → (R)-{5-[6-(1-Aza-bicyclo[2.2.2]oct-3-yloxy)-pyridazin-3-yl]-1H-indol-3-ylmethyl}-dimethyl-amine

HRID 1441422

Reaktionsgleichung

Reaktionsgleichung von HRID 1441422
[N:1]12[CH2:8][CH2:7][CH:4]([CH2:5][CH2:6]1)[C@@H:3]([O:9][C:10]1[N:15]=[N:14][C:13]([C:16]3[CH:17]=[C:18]4[C:22](=[CH:23][CH:24]=3)[NH:21][CH:20]=[CH:19]4)=[CH:12][CH:11]=1)[CH2:2]2.[CH2:25]=O.[CH3:27][NH:28][CH3:29]>O1CCOCC1.CC(O)=O>[N:1]12[CH2:8][CH2:7][CH:4]([CH2:5][CH2:6]1)[C@@H:3]([O:9][C:10]1[N:15]=[N:14][C:13]([C:16]3[CH:17]=[C:18]4[C:22](=[CH:23][CH:24]=3)[NH:21][CH:20]=[C:19]4[CH2:27][N:28]([CH3:25])[CH3:29])=[CH:12][CH:11]=1)[CH2:2]2

Komponenten

5

Edukt 3

HCID 674DimethylamineHCID 712FormaldehydeHCID 11151363Abt-107

Produkt 1

HCID 11314918(R)-{5-[6-(1-Aza-bicyclo[2.2.2]oct-3-yloxy)-pyridazin-3-yl]-1H-indol-3-ylmethyl}-dimethyl-amine

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 22565020HOAc dioxaneLösungsmittel

Versuchsvorschrift

The product of Example 9B (150 mg, 0.47 mmol) was treated with HCHO (Aldrich, 37%, 76 mg, 0.94 mmol) and dimethylamine (Aldrich, 42 mg, 0.94 mmol) in dioxane/HOAc (v. 1:1, 5 mL) at ambient temperature for 16 hours. It was then concentrated and the title product was purified by preparative HPLC (Xterra™, column, Xterra RP-18 5 μm, 30×100 mm. Eluting Solvent, MeCN/H2O (NH4HCO3, 0.1 M, pH=10) (v. 90/10 to 10/90 over 20 min.) Flow rate, 75 mL/min., uv, 250 nm) as solid (80 mg, 45%). 1H NMR (MeOH-D4, 300 MHz) 1.59-1.75 (m, 1H), 1.77-1.99 (m, 2H), 2.07-2.23 (m, 1H), 2.36-2.44 (m, 1H), 2.60-2.69 (m, 6H), 2.91-3.13 (m, 5H), 3.52-3.65 (m, 1H), 4.22 (s, 2H), 5.32-5.40 (m, 1H), 7.30 (d, J=9.5 Hz, 1H), 7.49 (s, 1H), 7.56 (d, J=8.5 Hz, 1H), 7.81 (dd, J=8.5, 1.7 Hz, 1H), 8.15 (d, J=9.5 Hz, 1H), 8.29 (s, 1H) ppm. MS (DCI/NH3) m/z 378(M+H)+.

Aufarbeitung

  1. concentrationIt was then concentrated
  2. customthe title product was purified by preparative HPLC (Xterra™, column, Xterra RP-18 5 μm, 30×100 mm. Eluting Solvent, MeCN/H2O (NH4HCO3, 0.1 M, pH=10) (v. 90/10 to 10/90 over 20 min.) Flow rate, 75 mL/min., uv, 250 nm) as solid (80 mg, 45%)

Quellen und Nachweise

ORD-Eintrag
ord-eb5531161d5742c2a64c1d33ce50501e
Quelldatensatz
uspto-grants-2010_02
Patentnummer
US07655657B2

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