3-Chloro-6-(2-chlorophenyl)-7-(4-chlorophenyl)-[1,2,4]triazolo[4,3-b]pyridazine → 1-(6-(2-Chlorophenyl)-7-(4-chlorophenyl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)-3-(ethylamino)pyrrolidine-3-carboxamide

HRID 2266308Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2266308
Cl[C:2]1[N:6]2[N:7]=[C:8]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[Cl:24])[C:9]([C:11]3[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=3)=[CH:10][C:5]2=[N:4][N:3]=1.[CH2:25]([NH:27][C:28]1([C:33]([NH2:35])=[O:34])[CH2:32][CH2:31][NH:30][CH2:29]1)[CH3:26]>C(O)CO>[Cl:24][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=1[C:8]1[C:9]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=2)=[CH:10][C:5]2[N:6]([C:2]([N:30]3[CH2:31][CH2:32][C:28]([NH:27][CH2:25][CH3:26])([C:33]([NH2:35])=[O:34])[CH2:29]3)=[N:3][N:4]=2)[N:7]=1

Komponenten

4

Edukt 2

HCID 579797573-Chloro-6-(2-chlorophenyl)-7-(4-chlorophenyl)-[1,2,4]triazolo[4,3-b]pyridazineHCID 686917293-(Ethylamino)pyrrolidine-3-carboxamide2×

Produkt 1

HCID 119930161-(6-(2-Chlorophenyl)-7-(4-chlorophenyl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)-3-(ethylamino)pyrrolidine-3-carboxamideAusbeute 26,9 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 174Ethylene GlycolLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

A suspension of 3-chloro-6-(2-chlorophenyl)-7-(4-chlorophenyl)-[1,2,4]triazolo[4,3-b]pyridazine (113 mg, 0.3 mmol) and 3-(ethylamino)pyrrolidine-3-carboxamide (94 mg, 0.6 mmol) in ethylene glycol (2 mL) was stirred at 110° C. for 2 h. Analysis by HPLC/MS indicated the reaction was not complete. Additional 3-(ethylamino)pyrrolidine-3-carboxamide (47 mg, 0.3 mmol) was added. The reaction continued at 110° C. for 1 h more. After cooling to room temperature, the reaction mixture was loaded onto a silica gel cartridge (12 g), eluted with a gradient of MeOH (0-6%) in CH2Cl2 to obtain 40 mg of desired product with 90% purity. The product was further purified using reverse phase preparative HPLC (Conditions: Phenomenex Luna 5μ C18 21.2×100 mm; Eluted with 40% to 90% B, 8 min gradient, 90% B hold for 3 min, (A=90% H2O, 10% MeOH, 0.1% trifluoroacetic acid and B=10% H2O, 90% MeOH, 0.1% trifluoroacetic acid); Flow rate at 20 mL/min, UV detection at 220 nm) to yield the product as a TFA salt. The product was dissolved in EtOAc, washed with saturated aqueous NaHCO3, water, saturated aqueous NaCl, dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was lyophilized in acetonitrile to afford 30 mg (20%) of the title compound as a yellow powder. HPLC/MS (method A): retention time=2.75 min, (M+H)+=496.2. 1H NMR (CDCl3, 400 MHz): δ 7.81 (s, 1H), 7.28-7.38 (m, 4H), 7.19-7.26 (m, 2H), 7.01-7.07 (m, 2H), 5.39 (s, 1H), 4.00-4.15 (m, 5H), 2.54-2.65 (m, 3H), 2.12 (m, 1H), 1.40-1.55 (m, 1H), 1.10 (t, J=7.09 Hz, 3H).

Aufarbeitung

  1. waitThe reaction continued at 110° C. for 1 h
  2. temperatureAfter cooling to room temperature
  3. washeluted with a gradient of MeOH (0-6%) in CH2Cl2

Quellen und Nachweise

ORD-Eintrag
ord-f2032d4b9095439dafab7a0a6c5f3caf
Quelldatensatz
uspto-grants-2010_12
Patentnummer
US07858639B2

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