Buchwald–Hartwig amination: 2-Chloro-4-iodo-5-(trifluoromethyl)pyridine → 2-(2-Chloro-5-(trifluoromethyl)pyridin-4-ylamino)-6-methoxy-N-methylbenzamide
85% yield, run at 90 °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-Chloro-4-iodo-5-(trifluoromethyl)pyridine | C₆H₂ClF₃IN | |
| Reactant | 2-amino-6-methoxy-N-methylbenzamide | C₉H₁₂N₂O₂ | |
| 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-Chloro-5-(trifluoromethyl)pyridin-4-ylamino)-6-methoxy-N-methylbenzamide | C₁₅H₁₃ClF₃N₃O₂ | 85.46% |
Conditions
- Temperature
- 90 °C
Yield
- 85% of 2-(2-Chloro-5-(trifluoromethyl)pyridin-4-ylamino)-6-methoxy-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-[(1,3-dimethylpyrazol-4-yl)amino]-5-(trifluoromethyl)-4-pyridyl]amino]-6-methoxy-N-methyl-benzamide75%
- 2-[2-Chloro-5-(trifluoromethyl)pyridin-4-ylamino]-N-methylbenzamide73%
- 2-[[2-Chloro-5-(trifluoromethyl)-4-pyridyl]amino]-5-fluoro-n-methoxy-benzamide40%
- 2-(2-(1,3-dimethyl-1H-pyrazol-5-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)-6-methoxy-N-methylbenzamide42%
Procedure
Copied from the source record, unedited
2-chloro-4-iodo-5-(trifluoromethyl)pyridine (7 g, 22.77 mmol), 2-amino-6-methoxy-N-methylbenzamide (4.31 g, 23.91 mmol), diacetoxypalladium (0.409 g, 1.82 mmol) (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (2.108 g, 3.64 mmol) and cesium carbonate (8.90 g, 27.32 mmol) were suspended in dioxane (75 ml). Argon was let to bubble into the dark purple blurred solution and the reaction mixture was heated to at 90 °C for 24h. (yellow suspension when temperature reached 70°C). The reaction mixture was allowed to cool to room temperature, diluted with DCM (some drop of MeOH) and filtered. Silica gel was added and solents were evaporated to afford the crude, which was purified twice* by flash chromatography on silica gel eluting with 10 to 60% ethyl acetate in petroleum ether. The solv
The source
This record comes from experimental reaction archive (ord-322e28476a6147ed99e484e5e4c5349d). Open the source and check it against what is on this page.
experimental reaction archive record ord-322e28476a6147ed99e484e5e4c5349d 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.
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