Buchwald–Hartwig amination: 2,4-Dichloropyridine → N-(4-chloro-2-pyridinyl)-1,3-oxazol-2-amine
3% yield, run at 140 °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 hydride | HNa | |
| 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 | 3.03% |
Conditions
- Temperature
- 140 °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% (this run) |
| 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% |
| 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
Objective: If deprotonation is rate-determining in this coupling quantitative deprotonation prior to subjection to coupling conditions should prove beneficial. To an oven dried microwave vial was added oxazol-2-amine (85 mg, 1.01 mmol) together with sodium hydride (40.5 mg, 1.01 mmol), the vial was capped and purged with nitrogen and dioxane (1 mL) was added. The mixture was then stirred at rt for 1 h (initially effervescence was observed but subsided within 20 min of stirring). To the above vial was added 2,4-dichloropyridine (0.109 mL, 1.01 mmol), TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (22.89 mg, 0.02 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (44.0 mg, 0.08 mmol) (Xantphos) as a solution in dioxane (2 mL) and the reaction mixture was heated to 140 °C for 1 h
The source
This record comes from experimental reaction archive (ord-76fdaa39a364497293ede72dc7b21aee). Open the source and check it against what is on this page.
experimental reaction archive record ord-76fdaa39a364497293ede72dc7b21aee 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
More Buchwald–Hartwig amination records
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