Water → Ethyl 4-oxo-1-{[6-(1,3-thiazol-4-yl)pyridin-3-yl]methyl}-1,4-dihydrocinnoline-3-carboxylate

HRID 242023Notes

Reaction equation

HRID 242023 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.C([Sn](CCCC)(CCCC)[C:30]1[N:31]=[CH:32][S:33][CH:34]=1)CCC.[F-].[Cs+].O>CN(C=O)C.[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[O:19]=[C:12]1[C:13]2[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=2)[N:9]([CH2:8][C:5]2[CH:6]=[N:7][C:2]([C:30]3[N:31]=[CH:32][S:33][CH:34]=3)=[CH:3][CH:4]=2)[N:10]=[C:11]1[C:20]([O:22][CH2:23][CH3:24])=[O:21]

Participants

8

Reactant 4

HCID 962WaterHCID 25953Cesium fluorideHCID 27632584-(Tri-n-butylstannyl)thiazoleHCID 86660005Ethyl 1-[(6-bromopyridin-3-yl)methyl]-4-oxo-1,4-dihydrocinnoline-3-carboxylate

Product 1

HCID 68796827Ethyl 4-oxo-1-{[6-(1,3-thiazol-4-yl)pyridin-3-yl]methyl}-1,4-dihydrocinnoline-3-carboxylate

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

Ethyl 1-[(6-bromopyridin-3-yl)methyl]-4-oxo-1,4-dihydrocinnoline-3-carboxylate (897 mg, 2.31 mmol), 4-(tributylstannanyl)-1,3-thiazole (1.04 g, 2.77 mmol, 1.2 equiv), copper(I) iodide (176 mg, 0.924 mmol, 0.4 equiv), cesium fluoride (702 mg, 4.62 mmol, 2 equiv) and tetrakis(triphenylphosphine)palladium(0) (534 mg, 0.462 mmol, 0.2 equiv) were combined in degassed N,N′-dimethylformamide (6 mL) and stirred for 1 hour at ambient temperature. The mixture was poured into water and extracted twice with ethyl acetate. The combined organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo. The residue was dissolved in chloroform, treated with potassium fluoride on Celite (8 g, 10 weight equiv) and after stirring vigorously for 24 hours, was filtered. The filtrate was concentrated in vacuo and the residue was purified by silica gel gradient chromatography (100:0 to 0:100; hexanes:ethyl acetate; then 100:0 to 95:5; chloroform:methanol), providing the titled compound.

Workup

  1. extractionextracted twice with ethyl acetate
  2. dry with materialThe combined organic extracts were dried with sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. dissolutionThe residue was dissolved in chloroform
  6. additiontreated with potassium fluoride on Celite (8 g, 10 weight equiv)
  7. stirringafter stirring vigorously for 24 hours
  8. filtrationwas filtered
  9. concentrationThe filtrate was concentrated in vacuo
  10. customthe residue was purified by silica gel gradient chromatography (100:0 to 0:100

Sources & evidence

ORD record
ord-de25fb9ff0594b00aeb41e4dc183403e
Source dataset
uspto-grants-2014_02
Patent number
US08653079B2

Reaction notes

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