Buchwald–Hartwig amination: 4-iodo-5-(trifluoromethyl)-N-(1,3,5-trimethylpyrazol-4-yl)pyridin-2-amine → N-methoxy-2-[[5-(trifluoromethyl)-2-[(1,3,5-trimethylpyrazol-4-yl)amino]pyridin-4-yl]amino]benzamide
89% 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 | 4-iodo-5-(trifluoromethyl)-N-(1,3,5-trimethylpyrazol-4-yl)pyridin-2-amine | C₁₂H₁₂F₃IN₄ | |
| Reactant | 2-Amino-N-methoxybenzamide | C₈H₁₀N₂O₂ | |
| 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 | N-methoxy-2-[[5-(trifluoromethyl)-2-[(1,3,5-trimethylpyrazol-4-yl)amino]pyridin-4-yl]amino]benzamide | C₂₀H₂₁F₃N₆O₂ | 89.15% |
Conditions
- Temperature
- 90 °C
Yield
- 89% of N-methoxy-2-[[5-(trifluoromethyl)-2-[(1,3,5-trimethylpyrazol-4-yl)amino]pyridin-4-yl]amino]benzamide.
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.
Procedure
Copied from the source record, unedited
2-amino-N-methoxybenzamide (541 mg, 3.26 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (166 mg, 0.29 mmol), cesium carbonate (1249 mg, 3.83 mmol) and diacetoxypalladium (38.7 mg, 0.17 mmol) were added to a stirred solution of 4-iodo-5-(trifluoromethyl)-N-(1,3,5-trimethyl-1H-pyrazol-4-yl)pyridin-2-amine (759 mg, 1.92 mmol) dissolved in dioxane (20 mL) in a µwave vial at RT. Argon was let to bubble in the mixture for 5 minutes and the resulting slurry was then stirred at 90 °C for 15 hours. Lcms showed complete reaction. The reaction mixture was allowed to cool to room temperature, diluted with dichloromethane, filtered, silica gel was added and the mixture was concentrated. The crude product was purified by flash chromatography on silica gel eluting with 30 to 100% ethyl
The source
This record comes from experimental reaction archive (ord-3db391e974974fdaa88ec87b15c89118). Open the source and check it against what is on this page.
experimental reaction archive record ord-3db391e974974fdaa88ec87b15c89118 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
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