Buchwald–Hartwig amination: 2,4-Dichloropyridine → N-(4-chloro-2-pyridinyl)-1,3-oxazol-2-amine
3% yield, run at 80 °C, as recorded by experimental reaction archive. The written procedure is below. One of 11 recorded runs making this product; all of them are compared below.
The atoms, from reactants to products
What was in the flask
| Role | Species | Formula | Yield |
|---|---|---|---|
| Reactant | 2,4-Dichloropyridine | C₅H₃Cl₂N | |
| Reactant | 2-Aminooxazole | C₃H₄N₂O | |
| Reagent | sodium phenoxide | C₆H₅NaO | |
| 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)-1,3-oxazol-2-amine | C₈H₆ClN₃O | 2.52% |
Conditions
- Temperature
- 80 °C
Yield
- 3% of N-(4-chloro-2-pyridinyl)-1,3-oxazol-2-amine.
Every recorded run making this product
11 runs of this class made the same product and differed in what else was in the flask. They are listed from the highest yield down, with this page's run marked.
| Reactants | Catalyst | Reagents | Solvent | Temp. | Time | Yield |
|---|---|---|---|---|---|---|
| 2,4-Dichloropyridine; 2-Aminooxazole | 1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine); Bis(dibenzylideneacetone)palladium | Potassium Carbonate | Anisole | 120 °C | — | 50% |
| 2,4-Dichloropyridine; 2-Aminooxazole | 1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine); Palladium (II) acetate | Cesium carbonate | 1,4-Dioxane | 100 °C | — | 11% |
| 2-Bromo-4-chloropyridine; 2-Aminooxazole | 1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine); Bis(dibenzylideneacetone)palladium | Cesium carbonate | 1,4-Dioxane | 140 °C | — | 8% |
| 2,4-Dichloropyridine; 2-Aminooxazole | 1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine); Bis(dibenzylideneacetone)palladium | Sodium hydride | 1,4-Dioxane | 140 °C | — | 3% |
| 2,4-Dichloropyridine; 2-Aminooxazole | 1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine); Bis(dibenzylideneacetone)palladium | sodium phenoxide | 1,4-Dioxane | 80 °C | — | 3% (this run) |
| 2,4-Dichloropyridine; 2-Aminooxazole | 1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine); Bis(dibenzylideneacetone)palladium | Cesium carbonate | 1,4-Dioxane | 140 °C | — | 2% |
| 2,4-Dichloropyridine; 2-Aminooxazole | 1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine); Palladium (II) acetate | Cesium carbonate | Dimethylacetamide | 100 °C | — | 2% |
| 2-Bromo-4-chloropyridine; 2-Aminooxazole | 1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine); Bis(dibenzylideneacetone)palladium | sodium phenoxide | 1,4-Dioxane | 170 °C | — | 1% |
| 2,4-Dichloropyridine; 2-Aminooxazole | Bis(3,5-bis(trifluoromethyl)phenyl)(3,6-dimethoxy-2',4',6'-tri(propan-2-yl)(1,1'-biphenyl)-2-yl)phosphane; Bis(dibenzylideneacetone)palladium | Cesium carbonate | 1,4-Dioxane | 140 °C | — | 0% |
| 2,4-Dichloropyridine; 2-Aminooxazole | 1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine); Bis(dibenzylideneacetone)palladium | Potassium Phosphate, Tribasic | 1,4-Dioxane | 160 °C | — | 0% |
| 2,4-Dichloropyridine; 2-Aminooxazole | Binap, (A+-)-; Bis(dibenzylideneacetone)palladium | sodium 2-methylpropan-2-olate | Toluene | 100 °C | — | 0% |
Procedure
Copied from the source record, unedited
To a flask containing 2,4-dichloropyridine (0.109 mL, 1.01 mmol), sodium phenolate (177 mg, 1.52 mmol), TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (11.60 mg, 0.01 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (17.59 mg, 0.03 mmol) (Xantphos), was added degassed dioxane (4 mL) and the mixture allowed to stir under nitrogen atmosphere for 5 min. To this solution was added oxazol-2-amine (94 mg, 1.11 mmol) and the reaction mixture was heated to 80 °C for three hours. A 1H NMR was measured of the crude reaction after the solvent had been removed. **This indicated the presence of significant amounts of 2,4-dichloropyridine as well as 2-amino oxazole**. LCMS of the crude reaction mixture at t= 90 min and at t= 3 h showed the desired product was present. The crude reaction mi
The source
This record comes from experimental reaction archive (ord-cab6249a1023430399dca1061d293aa8). Open the source and check it against what is on this page.
experimental reaction archive record ord-cab6249a1023430399dca1061d293aa8 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.
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Where to next
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