Buchwald–Hartwig amination: N-(1,3-dimethylpyrazol-5-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine → 2-[[2-[(2,5-dimethylpyrazol-3-yl)amino]-5-(trifluoromethyl)pyridin-4-yl]amino]-N,6-dimethoxybenzamide
72% yield, run at 90 °C, as recorded by experimental reaction archive. The written procedure is below. One of 3 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-N,6-dimethoxybenzamide | C₉H₁₂N₂O₃ | |
| 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)pyridin-4-yl]amino]-N,6-dimethoxybenzamide | C₂₀H₂₁F₃N₆O₃ | 71.59% |
Conditions
- Temperature
- 90 °C
Yield
- 72% of 2-[[2-[(2,5-dimethylpyrazol-3-yl)amino]-5-(trifluoromethyl)pyridin-4-yl]amino]-N,6-dimethoxybenzamide.
Every recorded run making this product
3 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.
| Catalyst | Reagents | Solvent | Temp. | Time | Yield |
|---|---|---|---|---|---|
| 1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine); Palladium (II) acetate | Cesium carbonate | 1,4-Dioxane | 90 °C | — | 72% (this run) |
| Binap, (A+-)-; Palladium (II) acetate | Cesium carbonate | 1,4-Dioxane | 90 °C | — | 0% |
| 1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine); Palladium (II) acetate | Potassium Carbonate | 1,4-Dioxane | 90 °C | — | 0% |
Procedure
Copied from the source record, unedited
N-(1,3-dimethyl-1H-pyrazol-5-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine (22.8 g, 59.67 mmol), 2-amino-N,6-dimethoxybenzamide (19.90 g, 101.43 mmol), diacetoxypalladium (0.670 g, 2.98 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (3.45 g, 5.97 mmol) and cesium carbonate (23.33 g, 71.60 mmol) were suspended in 1,4-dioxane (199 ml). The reaction was degased, purged with nitrogen and heated to 90 °C => _reaction turned to dark brown and solidified after ~15 minutes._ 1,4-dioxane (50 mL) was added and reaction was stirred at 90°C (internal temperature) overnight => _stirring became easier and mixture turned to beige/yellow then to dark green/grey during the night._ Reaction was concentrated to dryness. Residue was diluted with CH2Cl2 (300 mL) and water (300 mL). Aqueous wa
The source
This record comes from experimental reaction archive (ord-a7be07888e18485384d8c572f896eab3). Open the source and check it against what is on this page.
experimental reaction archive record ord-a7be07888e18485384d8c572f896eab3 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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Where to next
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