Buchwald–Hartwig amination: Ethyl 6-bromo-4-[(2,4-difluorophenyl)amino]-7-ethoxyquinoline-3-carboxylate → Ethyl 4-(2,4-difluoroanilino)-7-ethoxy-6-(4-propan-2-ylpiperazin-1-yl)quinoline-3-carboxylate
65% yield, run at 110 °C, as recorded by experimental reaction archive. The written procedure is below.
The atoms, from reactants to products
What was in the flask
| Role | Species | Formula | Yield |
|---|---|---|---|
| Reactant | Ethyl 6-bromo-4-[(2,4-difluorophenyl)amino]-7-ethoxyquinoline-3-carboxylate | C₂₀H₁₇BrF₂N₂O₃ | |
| Reactant | 1-Isopropylpiperazine | C₇H₁₆N₂ | |
| Reagent | Cesium carbonate | CCs₂O₃ | |
| Catalyst | Binap, (A+-)- | C₄₄H₃₂P₂ | |
| Catalyst | Bis(dibenzylideneacetone)palladium | C₅₁H₄₂O₃Pd₂ | |
| Product | Ethyl 4-(2,4-difluoroanilino)-7-ethoxy-6-(4-propan-2-ylpiperazin-1-yl)quinoline-3-carboxylate | C₂₇H₃₂F₂N₄O₃ | 65.39% |
Conditions
- Temperature
- 110 °C
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.
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.
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