1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → N-(4-((6-chloroimidazo[1,2-b]pyridazin-8-yl)amino)phenyl)-1-(4-fluorophenyl)-2-oxo-1,2-dihydro-3-pyridinecarboxamide

HRID 2239856Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2239856
[Cl:1][C:2]1[CH:3]=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([NH2:18])=[CH:14][CH:13]=2)[C:5]2[N:6]([CH:8]=[CH:9][N:10]=2)[N:7]=1.[F:19][C:20]1[CH:25]=[CH:24][C:23]([N:26]2[CH:31]=[CH:30][CH:29]=[C:28]([C:32](O)=[O:33])[C:27]2=[O:35])=[CH:22][CH:21]=1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1>CC#N.CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:11][C:12]2[CH:13]=[CH:14][C:15]([NH:18][C:32]([C:28]3[C:27](=[O:35])[N:26]([C:23]4[CH:22]=[CH:21][C:20]([F:19])=[CH:25][CH:24]=4)[CH:31]=[CH:30][CH:29]=3)=[O:33])=[CH:16][CH:17]=2)[C:5]2[N:6]([CH:8]=[CH:9][N:10]=2)[N:7]=1

Komponenten

7

Edukt 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 210815271-(4-Fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acidHCID 86611734N1-(6-chloroimidazo[1,2-b]pyridazin-8-yl)benzene-1,4-diamine

Produkt 1

HCID 59304423N-(4-((6-chloroimidazo[1,2-b]pyridazin-8-yl)amino)phenyl)-1-(4-fluorophenyl)-2-oxo-1,2-dihydro-3-pyridinecarboxamideAusbeute 9,8 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

To a 2 dram vial was added N1-(6-chloroimidazo[1,2-b]pyridazin-8-yl)benzene-1,4-diamine (0.078 g, 0.3 mmol, prepared as described in Example XV1, step 1a), 1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid (0.10 g, 0.45 mmol, prepared as described in Example XVII, step 1e2), EDCI (0.086 g, 0.45 mmol), HOBt (0.061 g, 0.45 mmol), TEA (0.12 ml, 0.9 mmol), DMF (0.8 ml) and CH3CN (1.5 ml). The reaction was allowed to stir around 50° C. for 12 hrs. Upon cooling, the solvent was removed in vacuo and diluted with methanol (2 ml). The solution was purified by HPLC (20-100% methanol gradient), which yielded 0.014 g of the title compound as a TFA salt. 1H NMR (400 MHz, CHLOROFORM-D) δ ppm 11.88 (1H, s), 8.70 (1H, dd, J=7.12, 2.03 Hz), 7.71-7.91 (3H, m), 7.67 (1H, s), 7.50-7.63 (1H, m), 7.10-7.43 (5H, m), 6.64 (1H, s), 6.56 (1H, t, J=7.12 Hz). LC/MS, m/e 475 (M+1). HPLC Rt, 2.82 min. YMC ODSC18 column (4.6×50 mm). 0%-100% B. Solvent B: (90% MeOH, 10% H2O, 0.1% TFA). Solvent A: (10% MeOH, 90% H2O, 0.1% TFA). Gradient, start % B=0, final % B=100, gradient time 4 min, hold at 100% B 1 min, flow rate 4 mL/min.

Aufarbeitung

  1. temperatureUpon cooling
  2. customthe solvent was removed in vacuo
  3. additiondiluted with methanol (2 ml)
  4. customThe solution was purified by HPLC (20-100% methanol gradient), which

Quellen und Nachweise

ORD-Eintrag
ord-1639899f4fd24d99bff7c2ce442c7d34
Quelldatensatz
uspto-grants-2010_05
Patentnummer
US07723336B2

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