Buchwald–Hartwig amination: 2,4-Dichloropyridine → N-(4-chloro-2-pyridinyl)-4,5-dimethyl-1,3-oxazol-2-amine
15% yield, run at 140 °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 | 2,4-Dichloropyridine | C₅H₃Cl₂N | |
| Reactant | 4,5-Dimethyloxazol-2-amine | C₅H₈N₂O | |
| Reagent | Cesium carbonate | CCs₂O₃ | |
| Catalyst | 1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) | C₃₉H₃₂OP₂ | |
| Catalyst | Bis(dibenzylideneacetone)palladium | C₅₁H₄₂O₃Pd₂ | |
| Solvent | 1,4-Dioxane | C₄H₈O₂ | |
| Product | N-(4-chloro-2-pyridinyl)-4,5-dimethyl-1,3-oxazol-2-amine | C₁₀H₁₀ClN₃O | 15.2% |
Conditions
- Temperature
- 140 °C
Yield
- 15% of N-(4-chloro-2-pyridinyl)-4,5-dimethyl-1,3-oxazol-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.
- N-(4-chloro-2-pyridinyl)-2,6-dimethylpyrimidin-4-amine61%
- 4-chloro-N-(2-methylpyrazol-3-yl)pyridin-2-amine60%
- N-(4-chloro-2-pyridinyl)-4-methylpyrimidin-2-amine58%
- N-(4-chloro-2-pyridinyl)pyrimidin-2-amine55%
- 4-chloro-N-pyridin-3-ylpyridin-2-amine51%
- N-(4-chloro-2-pyridinyl)-1,3-oxazol-2-amine50%
- Ethyl 2-[(4-chloro-2-pyridinyl)amino]-1,3-oxazole-5-carboxylate48%
- Ethyl 2-[(4-chloro-2-pyridinyl)amino]-1,3-oxazole-4-carboxylate37%
- N-(4-chloro-2-pyridinyl)-4-methyl-1,3-oxazol-2-amine28%
- N-(4-chloro-2-pyridinyl)-4-(trifluoromethyl)-1,3-oxazol-2-amine17%
- N-Benzyl-4-chloropyridin-2-amine0%
- 4-chloro-N-(2-methylpropyl)pyridin-2-amine0%
Procedure
Copied from the source record, unedited
Objective: To find out which substrates are efficient coupling partners, is there a robust link between how electron poor the substrate is and yield i.e. more electron poor aminooxazoles produce greater yields. Pd2(dba)3 (22.89 mg, 0.025 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (43.4 mg, 0.075 mmol), 2,4-dichloropyridine (148 mg, 1.00 mmol), cesium carbonate (652 mg, 2.00 mmol) and 4,5-dimethyloxazol-2-amine (112 mg, 1.00 mmol) were added to an oven dried microwave vial, the vial was capped and placed under an inert atmosphere, dioxane (4 mL) was added and the resulting mixture was heated to 140 °C for 1 h by microwave irradiation under a nitrogen atmosphere. The crude product was purified by flash silica chromatography, elution gradient 0 to 30% EtOAc in heptane. Pure frac
The source
This record comes from experimental reaction archive (ord-e66c732566f245d48f208bb758cb3489). Open the source and check it against what is on this page.
experimental reaction archive record ord-e66c732566f245d48f208bb758cb3489 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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