Water → Ethyl 1-[(6-methyl-2,3'-bipyridin-5-yl)methyl]-4-oxo-1,4-dihydropyrido[2,3-c]pyridazine-3-carboxylate

HRID 2067108Notes

Reaction equation

HRID 2067108 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([CH2:8][N:9]2[C:14]3[N:15]=[CH:16][CH:17]=[CH:18][C:13]=3[C:12](=S)[C:11]([C:20]([O:22][CH2:23][CH3:24])=[O:21])=[N:10]2)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C[C:32]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34][N:33]=1.[C:41](=O)(O)[O-].[Na+].[OH2:46]>O1CCCC1.[Cu]Cl.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[CH3:41][C:6]1[N:7]=[C:2]([C:37]2[CH:32]=[N:33][CH:34]=[CH:35][CH:36]=2)[CH:3]=[CH:4][C:5]=1[CH2:8][N:9]1[C:14]2[N:15]=[CH:16][CH:17]=[CH:18][C:13]=2[C:12](=[O:46])[C:11]([C:20]([O:22][CH2:23][CH3:24])=[O:21])=[N:10]1

Participants

9

Reactant 5

HCID 962WaterHCID 10796Cesium carbonateHCID 516892Sodium BicarbonateHCID 27630812-Methylpyridine-5-boronic acidHCID 86662099Ethyl 1-[(6-chloropyridin-3-yl)methyl]-4-thioxo-1,4-dihydropyrido[2,3-c]pyridazine-3-carboxylate

Product 1

HCID 66744617Ethyl 1-[(6-methyl-2,3'-bipyridin-5-yl)methyl]-4-oxo-1,4-dihydropyrido[2,3-c]pyridazine-3-carboxylate

Reagents, catalysts & solvents 3

HCID 62652Cuprous chlorideCatalystHCID 178418851HCID 178418851, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

Ethyl 1-[(6-chloropyridin-3-yl)methyl]-4-thioxo-1,4-dihydropyrido[2,3-c]pyridazine-3-carboxylate [(Example 5, Step 3), 335 mg, 0.972 mmol] was dissolved in tetrahydrofuran (15 mL), treated with an aqueous solution (3 mL) of cesium carbonate (792 mg, 2.43 mmol, 2.5 equiv), copper(I) chloride (96.0 mg, 0.972 mmol, 1 equiv), 2-methyl-5-pyridinylboronic acid (333 mg, 2.43 mmol, 2.5 equiv) and bis(tri-tert-butylphosphine)palladium(0) (99.0 mg, 0.194 mmol, 0.2 equiv). The mixture was placed into a preheated oil bath at 70° C. for 2 hours, cooled to ambient temperature, poured into sodium bicarbonate (50 mL, aqueous saturated) and water (100 mL) and then extracted with ethyl acetate (2×75 mL). The combined organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel gradient chromatography (100:0 to 0:100; hexanes:ethyl acetate containing 10% methanol), providing the titled compound as a light yellow solid.

Workup

  1. extractionextracted with ethyl acetate (2×75 mL)
  2. dry with materialThe combined organic extracts were dried with sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by silica gel gradient chromatography (100:0 to 0:100; hexanes:ethyl acetate containing 10% methanol)

Sources & evidence

ORD record
ord-2d46bf36122b4598a902658db0ab07fc
Source dataset
uspto-grants-2012_10
Patent number
US08293744B2

Reaction notes

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