Water → Ethyl 8-chloro-1-[(6-methylpyridin-3-yl)methyl]-4-oxo-1,4-dihydrocinnoline-3-carboxylate

HRID 449980Notes

Reaction equation

HRID 449980 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][C:17]=3[Cl:19])[C:12](=[O:20])[C:11]([C:21]([O:23][CH2:24][CH3:25])=[O:22])=[N:10]2)=[CH:4][CH:3]=1.[Cl-].[CH3:27][Zn+].O>O1CCCC1.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>[Cl:19][C:17]1[CH:16]=[CH:15][CH:14]=[C:13]2[C:18]=1[N:9]([CH2:8][C:5]1[CH:6]=[N:7][C:2]([CH3:27])=[CH:3][CH:4]=1)[N:10]=[C:11]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[C:12]2=[O:20]

Participants

6

Reactant 3

HCID 962WaterHCID 86659998Ethyl 1-[(6-bromopyridin-3-yl)methyl]-8-chloro-4-oxo-1,4-dihydrocinnoline-3-carboxylateHCID 178477797HCID 178477797, compound

Product 1

HCID 86660002Ethyl 8-chloro-1-[(6-methylpyridin-3-yl)methyl]-4-oxo-1,4-dihydrocinnoline-3-carboxylate

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

Ethyl 1-[6-bromopyridin-3-yl)methyl]-8-chloro-4-oxo-1,4-dihydrocinnoline-3-carboxylate [(Example 69, Step 1), 0.11 g, 0.25 mmol] was dissolved in tetrahydrofuran (1.5 mL), sparged under nitrogen and treated with methylzinc chloride (0.18 mL, 2.0 M tetrahydrofuran solution, 0.35 mmol, 1.4 equiv) and 1,1′bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (10 mg, 0.013 mmol, 0.05 equiv). After stirring for 15 minutes, tetrakis(triphenylphosphine)palladium(0) (58 mg, 0.050 mmol, 0.2 equiv) were added and the mixture was stirred at ambient temperature for an additional 2 hours. The mixture was poured into water, extracted twice with ethyl acetate and 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. customsparged under nitrogen
  2. stirringthe mixture was stirred at ambient temperature for an additional 2 hours
  3. extractionextracted twice with ethyl acetate
  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-c1de1d7d585e4b3db82b6bc5cbfbc5ed
Source dataset
uspto-grants-2013_07
Patent number
US08486946B2

Reaction notes

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