Buchwald–Hartwig amination: 2-Chloro-4-iodo-5-(trifluoromethyl)pyridine → 2-[2-Chloro-5-(trifluoromethyl)pyridin-4-ylamino]-N-methylbenzamide
73% 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-N-methylbenzamide | C₈H₁₀N₂O | |
| 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]-N-methylbenzamide | C₁₄H₁₁ClF₃N₃O | 73.43% |
Conditions
- Temperature
- 90 °C
Yield
- 73% of 2-[2-Chloro-5-(trifluoromethyl)pyridin-4-ylamino]-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-Chloro-5-(trifluoromethyl)pyridin-4-ylamino)-6-methoxy-N-methylbenzamide85%
- 2-[[2-[(1,3-dimethylpyrazol-4-yl)amino]-5-(trifluoromethyl)pyridin-4-yl]amino]-N-methylbenzamide77%
- 2-[[2-Chloro-5-(trifluoromethyl)-4-pyridyl]amino]-5-fluoro-n-methoxy-benzamide40%
- 2-[(2,5-Dichloro-4-pyridinyl)amino]-N-methylbenzamide32%
Procedure
Copied from the source record, unedited
2-chloro-4-iodo-5-(trifluoromethyl)pyridine (4.305 g, 14.00 mmol), 2-amino-N- methylbenzamide (2.103 g, 14.00 mmol), diacetoxypalladium (0.251 g, 1.12 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (1.296 g, 2.24 mmol) and cesium carbonate (5.47 g, 16.80 mmol) were mixed together in dioxane (80 mL). Reaction was degassed with argon and was stirred at 90 °C overnight (15 hours) under argon. Reaction was filtered, washed with CH2Cl2 and filtrate was concentrated to dryness. The crude product was purified by flash chromatography on silica gel eluting with 10 to 40% ethyl acetate in petroleum ether. The solvent was evaporated to dryness to afford 2-(2-chloro-5-(trifluoromethyl)pyridin-4-ylamino)-N-methylbenzamide (3.39 g, 73.4 %) as a white crystalline solid.
The source
This record comes from experimental reaction archive (ord-f216b4e86bcc4a2b8660bf0c5e130be5). Open the source and check it against what is on this page.
experimental reaction archive record ord-f216b4e86bcc4a2b8660bf0c5e130be5 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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