Buchwald–Hartwig amination: 2-Bromo-3-chloropyridine → 3-chloro-N-cyclobutylpyridin-2-amine
25% yield, run at 115 °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 | 2-Bromo-3-chloropyridine | C₅H₃BrClN | |
| Reactant | Cyclobutylamine | C₄H₉N | |
| Reagent | sodium 2-methylpropan-2-olate | C₄H₉NaO | |
| Catalyst | Binap, (A+-)- | C₄₄H₃₂P₂ | |
| Catalyst | Bis(dibenzylideneacetone)palladium | C₅₁H₄₂O₃Pd₂ | |
| Solvent | Toluene | C₇H₈ | |
| Product | 3-chloro-N-cyclobutylpyridin-2-amine | C₉H₁₁ClN₂ | 25.02% |
Conditions
- Temperature
- 115 °C
Yield
- 25% of 3-chloro-N-cyclobutylpyridin-2-amine.
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.
Procedure
Copied from the source record, unedited
Pd2(dba)3 (0.014 g, 0.02 mmol), 2,2'-bis(diphenylphosphanyl)-1,1'-binaphthalene (BINAP) (0.019 g, 0.03 mmol) and toluene (8 mL) was added to a flask. 2-bromo-3-chloropyridine (0.4 g, 2.08 mmol), cyclobutanamine (0.177 g, 2.49 mmol) and sodium 2-methylpropan-2-olate (0.348 g, 3.62 mmol) was added, the mixture bubbled with N2 for 5 min, then the reaction was heated to 115 °C in an oil-bath under nitrogen. LC-MS 1h: 33% product, 21% sm left. The reaction was cooled to rt and the solvent was evaporated. The residue was purified by automated flash chromatography on a 50g column. A gradient from 0% to 50% of EtOAc in heptane over 15CV was used as mobile phase. The product was collected using the wavelength 245 and 311 nm, relevant fractions pooled and evaporated to give 95 mg clear oil. 1H-N
The source
This record comes from experimental reaction archive (ord-a75ed1ad0e7c4cabb7785476d93cfc86). Open the source and check it against what is on this page.
experimental reaction archive record ord-a75ed1ad0e7c4cabb7785476d93cfc86 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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