Buchwald–Hartwig amination: 2,4-Dichloropyridine → N-(4-chloro-2-pyridinyl)-4-(trifluoromethyl)-1,3-oxazol-2-amine
17% 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 | 2-Amino-4-(trifluoromethyl)oxazole | C₄H₃F₃N₂O | |
| 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-(trifluoromethyl)-1,3-oxazol-2-amine | C₉H₅ClF₃N₃O | 17.45% |
Conditions
- Temperature
- 140 °C
Yield
- 17% of N-(4-chloro-2-pyridinyl)-4-(trifluoromethyl)-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)-4,5-dimethyl-1,3-oxazol-2-amine15%
- N-Benzyl-4-chloropyridin-2-amine0%
- 4-chloro-N-(2-methylpropyl)pyridin-2-amine0%
Procedure
Copied from the source record, unedited
Repeat of EN04881-41 to get pure sample of product in potentially higher isolated yield. cesium carbonate (652 mg, 2.00 mmol), Pd2(dba)3 (22.89 mg, 0.025 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (43.4 mg, 0.075 mmol), 4-(trifluoromethyl)oxazol-2-amine (152 mg, 1.00 mmol) and 2,4-dichloropyridine (148 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 at 140 °C for 1 h by microwave irradiation under a nitrogen atmosphere. Dichloromethane (10 mL) was added to the reaction mixture and the crude reaction mixture was adsorbed onto silica gel. The crude product was purified by flash silica chromatography, elution gradient 0 to 20% EtOAc in heptane. Pure
The source
This record comes from experimental reaction archive (ord-debb5d422e4240d09a376a4606e5e57f). Open the source and check it against what is on this page.
experimental reaction archive record ord-debb5d422e4240d09a376a4606e5e57f 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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