Buchwald–Hartwig amination: Methyl 4-((3-bromopyridin-2-yl)methoxy)benzoate → Methyl 4-((3-(4-methylpiperazin-1-yl)pyridin-2-yl)methoxy)benzoate
64% 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 | Methyl 4-((3-bromopyridin-2-yl)methoxy)benzoate | C₁₄H₁₂BrNO₃ | |
| Reactant | 1-Methylpiperazine | C₅H₁₂N₂ | |
| Reagent | Cesium carbonate | CCs₂O₃ | |
| Catalyst | Binap, (A+-)- | C₄₄H₃₂P₂ | |
| Catalyst | Bis(dibenzylideneacetone)palladium | C₅₁H₄₂O₃Pd₂ | |
| Solvent | Dimethylacetamide | C₄H₉NO | |
| Product | Methyl 4-((3-(4-methylpiperazin-1-yl)pyridin-2-yl)methoxy)benzoate | C₁₉H₂₃N₃O₃ | 64.22% |
Conditions
- Temperature
- 100 °C
Yield
- 64% of Methyl 4-((3-(4-methylpiperazin-1-yl)pyridin-2-yl)methoxy)benzoate.
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%
- 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%
- Ethyl 4-[(2,4-difluorophenyl)amino]-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
A mixture of methyl 4-((3-bromopyridin-2-yl)methoxy)benzoate (360 mg, 1.12 mmol), Pd2dba3 (205 mg, 0.22 mmol), BINAP (278 mg, 0.45 mmol), cesium carbonate (728 mg, 2.23 mmol) and 1-methylpiperazine (168 mg, 1.68 mmol) in DMA (10 mL) was stirred at 100 °C for overnight. Sat. NaHCO3 aq was added to the mixture, extracted with ethyl acetate three times, the combined organics were dried over anhydrous Na2SO4, filtered, the filtrate was conc. in vacuo, the residue was purified with ISCO (50% ethyl acetate in hexant to 100% ethyl acetate to 40% mthanol in ethyl acetate) to yield a brown oil as methyl 4-((3-(4-methylpiperazin-1-yl)pyridin-2-yl)methoxy)benzoate (245 mg, 64.2 %).
The source
This record comes from experimental reaction archive (ord-78ee6abad7ea4585a19ca47439cdac57). Open the source and check it against what is on this page.
experimental reaction archive record ord-78ee6abad7ea4585a19ca47439cdac57 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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