Buchwald–Hartwig amination: 2,5-Dichloro-4-iodopyridine → 2-(2,5-dichloropyridin-4-ylamino)-4-fluoro-N-methylbenzamide
35% yield, run at 100 °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 | 2,5-Dichloro-4-iodopyridine | C₅H₂Cl₂IN | |
| Reactant | 2-amino-4-fluoro-N-methylbenzamide | C₈H₉FN₂O | |
| Reagent | Cesium carbonate | CCs₂O₃ | |
| Catalyst | 1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) | C₃₉H₃₂OP₂ | |
| Catalyst | Palladium (II) acetate | C₄H₈O₄Pd | |
| Solvent | 1,4-Dioxane | C₄H₈O₂ | |
| Product | 2-(2,5-dichloropyridin-4-ylamino)-4-fluoro-N-methylbenzamide | C₁₃H₁₀Cl₂FN₃O | 34.87% |
Conditions
- Temperature
- 100 °C
Yield
- 35% of 2-(2,5-dichloropyridin-4-ylamino)-4-fluoro-N-methylbenzamide.
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.
- 2-[(2,5-dichloro-4-pyridinyl)amino]-N-(methyloxy)benzamide69%
- 8-[(2,5-Dichloropyridin-4-yl)amino]-2-methyl-3,4-dihydroisoquinolin-1-one43%
- 2-[(2,5-Dichloro-4-pyridinyl)amino]-N-methylbenzamide32%
- 2-(2,5-dichloropyridin-4-ylamino)-5-fluoro-N-methylbenzamide13%
- 2-[[2-[(2,5-dimethylpyrazol-3-yl)amino]-5-(trifluoromethyl)-4-pyridyl]amino]-4-fluoro-N-methyl-benzamide36%
Procedure
Copied from the source record, unedited
diacetoxypalladium (6.15 mg, 0.03 mmol) was added to a stirred suspension of 2,5-dichloro-4-iodopyridine (150 mg, 0.55 mmol), 2-amino-4-fluoro-N- methylbenzamide (92 mg, 0.55 mmol) (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (31.7 mg, 0.05 mmol) and cesium carbonate (268 mg, 0.82 mmol) in 1,4-dioxane (2.5 mL) under nitrogen. The resulting suspension was stirred at 100 °C for 16 hours. The mixture was cooled to RT; filtered the solvent was evaporated. The crude product was absorbed on silica gel and purified by flash chromatography on silica gel eluting with 20 to 80% ethyl acetate in petroleum ether. The solvent was evaporated to dryness to afford 2-(2,5-dichloropyridin-4-ylamino)-4-fluoro-N-methylbenzamide (60.0 mg, 34.9 %) as a beige solid.
The source
This record comes from experimental reaction archive (ord-6e62fa456f9543438c4d7ca789bf180e). Open the source and check it against what is on this page.
experimental reaction archive record ord-6e62fa456f9543438c4d7ca789bf180e 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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