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Buchwald–Hartwig amination, record ord-56b1f4bfeebc4b8ab990b9804e798aa7

One recorded run of this reaction. Below is what the source recorded, and nothing added to it.

verified record65% yield recordedNot balanced as writtenFrom experimental reaction archive

Reactants and products as the record gives them. Reagents, catalysts and solvents are listed below rather than drawn.

Open this record in the Reaction LabThe atom map, the animation and the records that run the same transformation.

What was in the flask

RoleSpeciesFormulaYield
ReactantEthyl 6-bromo-4-[(2,4-difluorophenyl)amino]-7-ethoxyquinoline-3-carboxylateC₂₀H₁₇BrF₂N₂O₃
Reactant1-IsopropylpiperazineC₇H₁₆N₂
ReagentCesium carbonateCCs₂O₃
CatalystBinap, (A+-)-C₄₄H₃₂P₂
CatalystBis(dibenzylideneacetone)palladiumC₅₁H₄₂O₃Pd₂
ProductEthyl 4-(2,4-difluoroanilino)-7-ethoxy-6-(4-propan-2-ylpiperazin-1-yl)quinoline-3-carboxylateC₂₇H₃₂F₂N₄O₃65.39%

The equation does not balance as written. That is usual for an experimental record: the source listed what it put in and what it measured, not a stoichiometric equation.

Conditions

Temperature
110 °C

Only the dimensions the source stated are listed. Anything absent here was not recorded, and it is not inferred from what the class usually needs.

Yield

  • 65% of Ethyl 4-(2,4-difluoroanilino)-7-ethoxy-6-(4-propan-2-ylpiperazin-1-yl)quinoline-3-carboxylate.

Procedure

Copied from the source record, unedited

To a solution of ethyl 6-bromo-4-(2,4-difluorophenylamino)-7-ethoxyquinoline-3-carboxylate (400 mg, 0.89 mmol) and 1-(Isopropyl)piperazine (254 µl, 1.77 mmol) in dioxane was added cesium carbonate (722 mg, 2.22 mmol), tris(dibenzylideneacetone)dipalladium(0) (40.6 mg, 0.04 mmol) and rac-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (55.2 mg, 0.09 mmol). Reaction vessel in oil bath set to 110 °C. 11am After 5 hours, MS shows product (major peak 499), and SM (minor peak 453). o/n, MS shows product peak. Reaction cooled, concentrated onto silica, and purified on ISCO. 40g column, 1:1 EA:Hex, then 100% EA. 289mg yellow solid. NMR (EN00180-62-1) supports product, but some oxidised BINAP impurity (LCMS 655).

The source

This record comes from experimental reaction archive (ord-56b1f4bfeebc4b8ab990b9804e798aa7). Open the source and check it against what is on this page.

  • experimental reaction archive record ord-56b1f4bfeebc4b8ab990b9804e798aa7 from dataset "750 AstraZeneca ELN dataset" (url: https://chemrxiv.org/engage/chemrxiv/article-details/60c9e3f37792a23bfdb2d471). No atom mapping is provided by the source.

    experimental record · quality medium · source

experimental reaction record.

How to read this record

This is one experiment, not a rule. It says that on one occasion these species were combined under these conditions and this came out. It does not say the reaction will give the same result on your substrate, and nothing on the page has been generalised into a claim that it would.

The pathway is a separate question, kept on separate pages. A mechanism here is the canonical arrow pushing for a class, run on real structures and labelled rule-derived. It is not evidence, and this record is not a mechanism.