(S)-6-(1-benzylpiperidin-3-ylamino)-8-(pyridin-2-ylamino)-N-(pyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide → (S)-6-(piperidin-3-ylamino)-8-(pyridin-2-ylamino)-N-(pyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide

HRID 1943455Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1943455
C([N:8]1[CH2:13][CH2:12][CH2:11][C@H:10]([NH:14][C:15]2[CH:16]=[C:17]([NH:33][C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][N:35]=3)[C:18]3[N:19]([C:21]([C:24]([NH:26][C:27]4[CH:32]=[CH:31][N:30]=[CH:29][CH:28]=4)=[O:25])=[CH:22][N:23]=3)[N:20]=2)[CH2:9]1)C1C=CC=CC=1>CO>[NH:8]1[CH2:13][CH2:12][CH2:11][C@H:10]([NH:14][C:15]2[CH:16]=[C:17]([NH:33][C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][N:35]=3)[C:18]3[N:19]([C:21]([C:24]([NH:26][C:27]4[CH:28]=[CH:29][N:30]=[CH:31][CH:32]=4)=[O:25])=[CH:22][N:23]=3)[N:20]=2)[CH2:9]1

Komponenten

3

Edukt 1

HCID 59624360(S)-6-(1-benzylpiperidin-3-ylamino)-8-(pyridin-2-ylamino)-N-(pyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide

Produkt 1

HCID 59624562(S)-6-(piperidin-3-ylamino)-8-(pyridin-2-ylamino)-N-(pyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamideAusbeute 20,8 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel

Versuchsvorschrift

A Parr bottle was charged with (S)-6-(1-benzylpiperidin-3-ylamino)-8-(pyridin-2-ylamino)-N-(pyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide 37B (0.055 g, 0.106 mmol), and dissolved in 30 mL of methanol with heating. The solution was purged with nitrogen and 200 mgs of 10% Pd/C was added. The resulting mixture was hydrogenated overnight on a Parr apparatus at 50 psi hydrogen. The mixture was filtered through celite and concentrated in vacuo. The resulting residue was dissolved in 2 mL methanol and 2 mL Solvent B (90% MeOH, 10% water, 0.1% TFA). One drop of TFA was added to the solution and the sample was split into 3 equal volumes and purified by reverse phase preparative HPLC on a Phenx Luna Axia Column 5u (21.2×100 mm) Solvent A (10% MeOH, 90% water, 0.1% TFA), Solvent B (90% MeOH, 10% water, 0.1% TFA) 20-100% solvent B gradient, 20 mL/min, 220 nM UV detection to provide (S)-6-(piperidin-3-ylamino)-8-(pyridin-2-ylamino)-N-(pyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide (0.0169 g, 0.022 mmol, 20.69% yield). 1H NMR (500 MHz, CD3OD) δ ppm 8.58 (2 H, m), 8.26 (1H, m), 8.19 (2H, m), 8.13 (1H, s), 8.02 (1H, s), 7.66 (1H, m), 7.08 (1H, m), 6.93 (1H, m), 4.18 (1H, m), 3.433 (1H, m), 3.27 (1H, m), 3.06 (2H, m), 2.14 (1H, m), 2.04 (1H, m), 1.86 (2H, m). LC/MS: HPLC Retention time: 2.15 min, MS: 430 (M+1) (Shimidazu LC, Waters Sunfire C-18 column (4.65×50 mm, 5 um, 0-100% Solvent B, 4 min gradient, 4 mL/min, 220 UV detection. Solvent A: 10% MeOH/90% Water/0.1% TFA, Solvent B 90% MeOH/10% Water/0.1% TFA.)

Aufarbeitung

  1. temperaturewith heating
  2. customThe solution was purged with nitrogen and 200 mgs of 10% Pd/C
  3. additionwas added
  4. filtrationThe mixture was filtered through celite and
  5. concentrationconcentrated in vacuo
  6. dissolutionThe resulting residue was dissolved in 2 mL methanol
  7. additionOne drop of TFA was added to the solution
  8. customthe sample was split into 3 equal volumes
  9. custompurified by reverse phase preparative HPLC on a Phenx Luna Axia Column 5u (21.2×100 mm) Solvent A (10% MeOH, 90% water, 0.1% TFA), Solvent B (90% MeOH, 10% water, 0.1% TFA) 20-100% solvent B gradient, 20 mL/min, 220 nM UV detection

Quellen und Nachweise

ORD-Eintrag
ord-09d959451c794086bee1db8636fb386c
Quelldatensatz
uspto-grants-2013_03
Patentnummer
US08389527B2

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