Tetrahydrofuran → 3-(6-(4-(tert-Butoxycarbonyl)piperazin-1-yl)pyridin-3-yl)-8-morpholinoimidazo[1,2-b]pyridazine-2-carboxylic acid

HRID 718594Notes

Reaction equation

HRID 718594 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[N:19]=[CH:18][C:17]([C:20]3[N:24]4[N:25]=[CH:26][CH:27]=[C:28]([N:29]5[CH2:34][CH2:33][O:32][CH2:31][CH2:30]5)[C:23]4=[N:22][C:21]=3[C:35]([O:37]CC)=[O:36])=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1COCC1.[OH-].[Na+]>CO>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[N:19]=[CH:18][C:17]([C:20]3[N:24]4[N:25]=[CH:26][CH:27]=[C:28]([N:29]5[CH2:34][CH2:33][O:32][CH2:31][CH2:30]5)[C:23]4=[N:22][C:21]=3[C:35]([OH:37])=[O:36])=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 14798Sodium Hydroxide2×HCID 117728679Ethyl 3-(6-(4-(tert-butoxycarbonyl)piperazin-1-yl)pyridin-3-yl)-8-morpholinoimidazo[1,2-b]pyridazine-2-carboxylate

Product 1

HCID 1177284223-(6-(4-(tert-Butoxycarbonyl)piperazin-1-yl)pyridin-3-yl)-8-morpholinoimidazo[1,2-b]pyridazine-2-carboxylic acid

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Compound 20b (2.07 g, 3.85 mmol) was placed in a 100 mL round bottom flask equipped with a stir bar and then THF (35 mL) was added. 1M NaOH (7.7 mL) was added and the reaction was stirred at rt for 3 d. Additional 1 M NaOH (8 mL) was added followed by addition of MeOH until the reaction went homogeneous. The reaction was stirred for 4 h and then the solvent was removed under reduced pressure. The residue was dissolved in water (100 mL) and extracted with Et2O (2×20 mL). The aqueous phase was acidified with 10% citric acid resulting in a precipitate. The mixture was diluted with DCM (100 mL) and the organic phase was separated. The aqueous layer was extracted with DCM (3×50 mL) and then the combined organic extracts were washed with water (30 mL) and dried over MgSO4. The solution was filtered and the solvent was removed under reduced pressure to afford compound 20c. 1H-NMR (400 MHz, CDCl3) δ (ppm): 8.58 (d, J=2.0 Hz, 1H), 8.06 (d, J=5.6 Hz, 1H), 7.91 (dd, J=8.9, 2.3 Hz, 1H), 6.76 (d, J=8.8 Hz, 1H), 6.14 (d, J=5.9 Hz, 1H), 3.97-4.06 (m, 4H), 3.90-3.97 (m, 4H), 3.61-3.70 (m, 4H), 3.52-3.60 (m, 4H), 1.50 (s, 9H).

Workup

  1. customequipped with a stir bar
  2. stirringThe reaction was stirred for 4 h
  3. customthe solvent was removed under reduced pressure
  4. dissolutionThe residue was dissolved in water (100 mL)
  5. extractionextracted with Et2O (2×20 mL)
  6. additionThe mixture was diluted with DCM (100 mL)
  7. customthe organic phase was separated
  8. extractionThe aqueous layer was extracted with DCM (3×50 mL)
  9. washthe combined organic extracts were washed with water (30 mL)
  10. dry with materialdried over MgSO4
  11. filtrationThe solution was filtered
  12. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-bb1e730aba674085958d7922fa04d19a
Source dataset
uspto-grants-2015_11
Patent number
US09193736B2

Reaction notes

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