6-chloro-8-((4-methoxybenzyl)(phenyl)amino)-N-(2-methylpyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide → HCID 178428625, Verbindung

HRID 1943499

Reaktionsgleichung

Reaktionsgleichung von HRID 1943499
Cl[C:2]1[CH:3]=[C:4]([N:21](CC2C=CC(OC)=CC=2)[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:5]2[N:6]([C:8]([C:11]([NH:13][C:14]3[CH:19]=[CH:18][N:17]=[C:16]([CH3:20])[CH:15]=3)=[O:12])=[CH:9][N:10]=2)[N:7]=1.[C@H:37]1([NH2:44])[CH2:42][CH2:41][C@H:40]([NH2:43])[CH2:39][CH2:38]1>C(O)(C(F)(F)F)=O>[NH2:43][C@H:40]1[CH2:41][CH2:42][C@H:37]([NH:44][C:2]2[CH:3]=[C:4]([NH:21][C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=3)[C:5]3[N:6]([C:8]([C:11]([NH:13][C:14]4[CH:19]=[CH:18][N:17]=[C:16]([CH3:20])[CH:15]=4)=[O:12])=[CH:9][N:10]=3)[N:7]=2)[CH2:38][CH2:39]1

Komponenten

4

Edukt 2

HCID 596246286-chloro-8-((4-methoxybenzyl)(phenyl)amino)-N-(2-methylpyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamideHCID 178511674HCID 178511674, Verbindung

Produkt 1

HCID 178428625HCID 178428625, VerbindungAusbeute 48,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6422Trifluoroacetic acidLösungsmittel

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

6-Chloro-8-((4-methoxybenzyl)(phenyl)amino)-N-(2-methylpyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide (100 mg, 0.201 mmol) and (trans)-cyclohexane-1,4-diamine (9459 mg, 4.016 mmol) were heated at 160° C. for 1 hour. The reaction mixture was dissolved in TFA (5 mL) and heated at 70° C. for 2 hours. The reaction mixture was concentrated, dissolved in methanol and purified by preparative HPLC (Phenomenex Axia Luna 5 micron 30×100 mm) 30% B (Solvent B=90% MeOH-10% H2O-0.1% TFA) to 100% B in A (Solvent A=10% MeOH-90% H2O-0.1% TFA) to afford 6-((trans-4-aminocyclohexyl)amino)-8-anilino-N-(2-methyl-4-pyridinyl)imidazo[1,2-b]pyridazine-3-carboxamide (39 mg, 48.5% yield) as a white solid. LC/MS (Phenomenex Luna 5 micron C18 4.6×30 mm, 0 to 100 B in 2 min with 1 min hold time, Flow rate=5 mL/min, detection at 254 nm, Solvent A: 10% methanol/90% water/0.1% TFA; Solvent B: 10% water/90% methanol/0.1% TFA). Rt=1.320 minutes, [M+H]=457.28. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.35-11.58 (1H, m), 9.33 (1H, s), 8.48-8.74 (1H, m), 8.14 (1H, s), 7.93-8.04 (1H, m), 7.87 (3H, d, J=4.28 Hz), 7.59-7.81 (1H, m), 7.31-7.52 (3H, m), 7.07-7.26 (1H, m), 6.87-7.06 (1H, m), 6.29 (1H, s), 3.53-3.77 (1H, m), 2.93-3.22 (1H, m), 2.65 (3H, s), 2.05-2.25 (2H, m), 1.87-2.09 (2H, m), 1.09-1.52 (4H, m).

Aufarbeitung

  1. concentrationThe reaction mixture was concentrated
  2. dissolutiondissolved in methanol
  3. custompurified by preparative HPLC (Phenomenex Axia Luna 5 micron 30×100 mm) 30% B (Solvent B=90% MeOH-10% H2O-0.1% TFA) to 100% B in A (Solvent A=10% MeOH-90% H2O-0.1% TFA)

Quellen und Nachweise

ORD-Eintrag
ord-bac16354b9ab45a894200c0316c0e845
Quelldatensatz
uspto-grants-2013_03
Patentnummer
US08389527B2

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