Buchwald–Hartwig amination: N-(1,3-dimethylpyrazol-5-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine → 2-(2-(1,3-dimethyl-1H-pyrazol-5-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)-6-methoxy-N-methylbenzamide
42% yield, run at 95 °C, as recorded by experimental reaction archive. The written procedure is below. One of 2 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 | N-(1,3-dimethylpyrazol-5-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine | C₁₁H₁₀F₃IN₄ | |
| 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-(1,3-dimethyl-1H-pyrazol-5-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)-6-methoxy-N-methylbenzamide | C₂₀H₂₁F₃N₆O₂ | 41.58% |
Conditions
- Temperature
- 95 °C
Yield
- 42% of 2-(2-(1,3-dimethyl-1H-pyrazol-5-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)-6-methoxy-N-methylbenzamide.
Every recorded run making this product
2 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-(2-Chloro-5-(trifluoromethyl)pyridin-4-ylamino)-6-methoxy-N-methylbenzamide; 1,3-Dimethyl-1H-pyrazol-5-amine | 1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine); Palladium (II) acetate | Cesium carbonate | 1,4-Dioxane | 90 °C | — | 44% |
| N-(1,3-dimethylpyrazol-5-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine; 2-amino-6-methoxy-N-methylbenzamide | 1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine); Palladium (II) acetate | Cesium carbonate | 1,4-Dioxane | 95 °C | — | 42% (this run) |
Procedure
Copied from the source record, unedited
2-amino-6-methoxy-N-methylbenzamide (19.45 g, 107.95 mmol), N-(1,3-dimethyl-1H-pyrazol-5-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine (27.5 g, 71.97 mmol) (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (4.16 g, 7.20 mmol) diacetoxypalladium (0.808 g, 3.60 mmol) and cesium carbonate (42.2 g, 129.54 mmol) were suspended in dioxane (300 mL). The reaction was degased, purged with argon sereval times and heated to 95 °C overnight. The reaction mixture was allowed to cool to rt, the insolubles were removed by filtration, washed with EtOAc and the filtrate was concentrated. The resulting residue was triturated with dichloromethane (150 ml), filtered, washed with DCM to give EN03299-47-01 (8.5 g, 19.57 mmol, 27.2 %) The filtrate was purified by flash chromatography on silica gel elut
The source
This record comes from experimental reaction archive (ord-62ffd954c4be4ad5b0533c19b263b236). Open the source and check it against what is on this page.
experimental reaction archive record ord-62ffd954c4be4ad5b0533c19b263b236 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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