(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 1943455Notes

Reaction equation

HRID 1943455 reaction equation
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

Participants

3

Reactant 1

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

Product 1

HCID 59624562(S)-6-(piperidin-3-ylamino)-8-(pyridin-2-ylamino)-N-(pyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamideYield 20.8%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

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.)

Workup

  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

Sources & evidence

ORD record
ord-09d959451c794086bee1db8636fb386c
Source dataset
uspto-grants-2013_03
Patent number
US08389527B2

Reaction notes

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