Buchwald–Hartwig amination: 1-Methylpiperazine → Ethyl 4-[(2,4-difluorophenyl)amino]-6-(4-methylpiperazin-1-yl)quinoline-3-carboxylate
0% yield, run at 100 °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 | CCOC(=O)c1cnc2ccc(Br)cc2c1Nc1ccc(F)cc1F.Cl | C₁₈H₁₄BrClF₂N₂O₂ | |
| Reactant | 1-Methylpiperazine | C₅H₁₂N₂ | |
| Reagent | Cesium carbonate | CCs₂O₃ | |
| Catalyst | Binap, (A+-)- | C₄₄H₃₂P₂ | |
| Catalyst | Bis(dibenzylideneacetone)palladium | C₅₁H₄₂O₃Pd₂ | |
| Solvent | 1,4-Dioxane | C₄H₈O₂ | |
| Product | Ethyl 4-[(2,4-difluorophenyl)amino]-6-(4-methylpiperazin-1-yl)quinoline-3-carboxylate | C₂₃H₂₄F₂N₄O₂ | 0% |
Conditions
- Temperature
- 100 °C
Yield
- 0% of Ethyl 4-[(2,4-difluorophenyl)amino]-6-(4-methylpiperazin-1-yl)quinoline-3-carboxylate.
Other recorded runs with the same starting material
No other run in the library makes this product. These runs of the same class start from one of the same reactants, which is the nearest company this record has.
- N-[5-(4-methylpiperazin-1-yl)pyrazin-2-yl]acetamide80%
- Methyl 3-(4-methyl-1-piperazinyl)-5-nitrobenzoate65%
- Methyl 4-((3-(4-methylpiperazin-1-yl)pyridin-2-yl)methoxy)benzoate64%
- 1-(4-Chloro-2-methoxyphenyl)-4-methylpiperazine64%
- 4-(4-Methyl-1-piperazinyl)phenol51%
- 1-(5-Bromopyridin-3-yl)-4-methylpiperazine21%
- 1-(3-bromo-1-methyl-1H-1,2,4-triazol-5-yl)-4-methylpiperazine0%
- Ethyl 4-[(2,4-dichlorophenyl)amino]-7-methoxy-6-(4-methylpiperazin-1-yl)quinoline-3-carboxylate0%
- N-[5-(1H-imidazol-2-yl)-2-methylphenyl]-4-[[3-(4-methylpiperazin-1-yl)-2-pyridinyl]methoxy]benzamide0%
- 1-(4-Chloro-2-methoxyphenyl)-4-methylpiperazine0%
Procedure
Copied from the source record, unedited
To a solution of ethyl 6-bromo-4-(2,4-difluorophenylamino)quinoline-3-carboxylate hydrochloride (505 mg, 1.14 mmol) and 1-methylpiperazine (0.189 mL, 1.71 mmol) in dioxane (10 mL) was added cesium carbonate (1113 mg, 3.41 mmol), tris(dibenzylideneacetone)dipalladium(0) (52.1 mg, 0.06 mmol) and rac-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (70.9 mg, 0.11 mmol). Reaction vessel in oil bath set to 100 °C. 3pm o/n - 20 hours, LCMS shows mostly SM (408), trace of product (427). Heating stopped after 24 hours. 8/6/08 - Additional portions of Pd cat, BINAP and Me piperazine added, and reaction returned to oil bath at 105C. o/n - Reaction more advanced, but still mostly SM. From past experience, Buchwald coupling may be more successful if SM is purified on silica column first. Discarded
The source
This record comes from experimental reaction archive (ord-cf1404eae16044b48089126b4e1896af). Open the source and check it against what is on this page.
experimental reaction archive record ord-cf1404eae16044b48089126b4e1896af 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.
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.
Where to next
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