Buchwald–Hartwig amination: 2-Bromo-4-chloropyridine → N-(4-chloro-2-pyridinyl)-1,3-oxazol-2-amine
8% 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-Bromo-4-chloropyridine | C₅H₃BrClN | |
| Reactant | 2-Aminooxazole | C₃H₄N₂O | |
| 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)-1,3-oxazol-2-amine | C₈H₆ClN₃O | 7.67% |
Conditions
- Temperature
- 140 °C
Yield
- 8% 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% (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 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% |
| 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: To find out if the 2-bromopyridine is a more efficient coupling partner than the chloro analogue. Pd2(dba)3 (22.89 mg, 0.025 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (43.4 mg, 0.075 mmol), 2-bromo-4-chloropyridine (192 mg, 1.00 mmol), cesium carbonate (652 mg, 2.00 mmol) and oxazol-2-amine (84 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. The crude product was purified by flash silica chromatography, elution gradient 0 to 30% EtOAc in heptane. Pure fractions were evaporated to dryness to afford N-(4-chloropyridin-2-yl)oxazol-2-amine (15.00 mg, 7.67 %) as a white
The source
This record comes from experimental reaction archive (ord-25a2d29381d0432e90a88d041ce4da72). Open the source and check it against what is on this page.
experimental reaction archive record ord-25a2d29381d0432e90a88d041ce4da72 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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