Cesium carbonate → ethyl 1-{[6-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)methyl}-4-oxo-1,4-dihydrocinnoline-3-carboxylate

HRID 449989Notes

Reaction equation

HRID 449989 reaction equation
Br[C:2]1[N:7]=[CH:6][C:5]([CH2:8][N:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12](=[O:19])[C:11]([C:20]([O:22][CH2:23][CH3:24])=[O:21])=[N:10]2)=[CH:4][CH:3]=1.[CH3:25][N:26]1[CH:30]=[C:29](B2OC(C)(C)C(C)(C)O2)[CH:28]=[N:27]1.C(=O)([O-])[O-].[Cs+].[Cs+].C(=O)(O)[O-].[Na+]>O1CCCC1.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>[CH3:25][N:26]1[CH:30]=[C:29]([C:2]2[N:7]=[CH:6][C:5]([CH2:8][N:9]3[C:18]4[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=4)[C:12](=[O:19])[C:11]([C:20]([O:22][CH2:23][CH3:24])=[O:21])=[N:10]3)=[CH:4][CH:3]=2)[CH:28]=[N:27]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 516892Sodium BicarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 86660005Ethyl 1-[(6-bromopyridin-3-yl)methyl]-4-oxo-1,4-dihydrocinnoline-3-carboxylate

Product 1

HCID 86660008ethyl 1-{[6-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)methyl}-4-oxo-1,4-dihydrocinnoline-3-carboxylate

Reagents, catalysts & solvents 2

HCID 178418851HCID 178418851, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

Ethyl 1-[(6-bromopyridin-3-yl)methyl]-4-oxo-1,4-dihydrocinnoline-3-carboxylate [(Example 83, Step 1), 748 mg, 1.93 mmol] and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (682 mg, 3.28 mmol, 1.7 equiv) were suspended in tetrahydrofuran (15 mL) and treated with an aqueous solution (1.5 mL) of cesium carbonate (1.26 g, 3.85 mmol, 2 equiv). The mixture was sparged under nitrogen, treated with bis(tri-tert-butylphosphine)palladium(0) (197 mg, 0.385 mmol, 0.2 equiv) and placed in an oil bath preheated to 80° C. for 1 hour. The mixture was cooled to ambient temperature, poured into sodium bicarbonate (75 mL, aqueous saturated) and extracted with ethyl acetate (2×100 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), providing the titled compound.

Workup

  1. customThe mixture was sparged under nitrogen
  2. customplaced in an oil bath
  3. extractionextracted with ethyl acetate (2×100 mL)
  4. dry with materialThe combined organic extracts were dried with sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel gradient chromatography (100:0 to 0:100; hexanes:ethyl acetate)

Sources & evidence

ORD record
ord-2a2d2d8f367648d5b336f17ded352a66
Source dataset
uspto-grants-2013_07
Patent number
US08486946B2

Reaction notes

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