Buchwald–Hartwig amination: 1,3-Dimethyl-1H-pyrazol-5-amine → 2-[[2-[(2,5-dimethylpyrazol-3-yl)amino]-5-(trifluoromethyl)-4-pyridyl]amino]-4-fluoro-N-methyl-benzamide
56% yield, run at 90 °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 | CNC(=O)c1ccc(F)cc1Nc1cc(Cl)ncc1C(F)(F)F | C₁₄H₁₀ClF₄N₃O | |
| Reactant | 1,3-Dimethyl-1H-pyrazol-5-amine | C₅H₉N₃ | |
| 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-[(2,5-dimethylpyrazol-3-yl)amino]-5-(trifluoromethyl)-4-pyridyl]amino]-4-fluoro-N-methyl-benzamide | C₁₉H₁₈F₄N₆O | 55.5% |
Conditions
- Temperature
- 90 °C
Yield
- 56% of 2-[[2-[(2,5-dimethylpyrazol-3-yl)amino]-5-(trifluoromethyl)-4-pyridyl]amino]-4-fluoro-N-methyl-benzamide.
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 |
|---|---|---|---|---|---|---|
| C14H10ClF4N3O; 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 | — | 56% (this run) |
| N-(1,3-dimethylpyrazol-5-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine; 2-amino-4-fluoro-N-methylbenzamide | 1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine); Palladium (II) acetate | Cesium carbonate | 1,4-Dioxane | 100 °C | — | 36% |
Procedure
Copied from the source record, unedited
2-(2-chloro-5-(trifluoromethyl)pyridin-4-ylamino)-4-fluoro-N-methylbenzamide (8.9 g, 25.60 mmol), 1,3-dimethyl-1H-pyrazol-5-amine (3.41 g, 30.72 mmol), diacetoxypalladium (0.460 g, 2.05 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (2.370 g, 4.10 mmol) and cesium carbonate (10.01 g, 30.72 mmol) were suspended in 1,4-dioxane (111 ml). The reaction was degased, purged with nitrogen and heated to 90°C (internal temperature) for 4 hours _._ Reaction was concentrated to dryness. Residue was diluted with CH2Cl2/MeOH 9/1 (200 mL) and water (200 mL). Aqueous was extracted with CH2Cl2/MeOH 9/1 (100 mL). Combined organic layers were dried over MgSO4 and concentrated to dryness. The crude product was purified by flash chromatography on silica gel eluting with 0 to 5% methanol in et
The source
This record comes from experimental reaction archive (ord-a11b668f474546c6bffcfc85e307c94b). Open the source and check it against what is on this page.
experimental reaction archive record ord-a11b668f474546c6bffcfc85e307c94b 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
More Buchwald–Hartwig amination records
Other runs of this class, one page per distinct transformation.
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