Buchwald–Hartwig amination: 2-[2-Chloro-5-(trifluoromethyl)pyridin-4-ylamino]-N-methylbenzamide → N-methyl-2-[[5-(trifluoromethyl)-2-[(1,3,5-trimethylpyrazol-4-yl)amino]pyridin-4-yl]amino]benzamide
24% yield, run at 100 °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-[2-Chloro-5-(trifluoromethyl)pyridin-4-ylamino]-N-methylbenzamide | C₁₄H₁₁ClF₃N₃O | |
| Reactant | 1,3,5-trimethyl-1H-pyrazol-4-amine | C₆H₁₁N₃ | |
| 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-methyl-2-[[5-(trifluoromethyl)-2-[(1,3,5-trimethylpyrazol-4-yl)amino]pyridin-4-yl]amino]benzamide | C₂₀H₂₁F₃N₆O | 24.43% |
Conditions
- Temperature
- 100 °C
Yield
- 24% of N-methyl-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-(2-chloro-5-(trifluoromethyl)pyridin-4-ylamino)-N-methylbenzamide (100 mg, 0.30 mmol), 1,3,5-trimethyl-1H-pyrazol-4-amine (76 mg, 0.61 mmol), cesium carbonate (119 mg, 0.36 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (28.1 mg, 0.05 mmol) and diacetoxypalladium (5.45 mg, 0.02 mmol) were suspended in dioxane (1.5 mL) and sealed into a tube. The reaction was degased, purged with nitrogen and heated to 100 °C for 18 hours. Reaction was filtered. The reaction mixture was purified by preparative HPLC using a Waters X-Bridge reverse-phase column (C-18, 5 microns silica, 19 mm diameter, 100 mm length, flow rate of 40 ml / minute) and decreasingly polar mixtures of water (containing 0.2% ammonium carbonate) and acetonitrile as eluent. The fractions containing the desired comp
The source
This record comes from experimental reaction archive (ord-61d7c948e79b47fd9fd72f241c80d4f1). Open the source and check it against what is on this page.
experimental reaction archive record ord-61d7c948e79b47fd9fd72f241c80d4f1 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
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