Buchwald–Hartwig amination: N-(1,3-dimethylpyrazol-4-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine → 2-[[2-[(1,3-dimethylpyrazol-4-yl)amino]-5-(trifluoromethyl)pyridin-4-yl]amino]-N-methylbenzamide
77% 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 | N-(1,3-dimethylpyrazol-4-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine | C₁₁H₁₀F₃IN₄ | |
| Reactant | 2-Amino-N-methylbenzamide | C₈H₁₀N₂O | |
| 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-dimethylpyrazol-4-yl)amino]-5-(trifluoromethyl)pyridin-4-yl]amino]-N-methylbenzamide | C₁₉H₁₉F₃N₆O | 76.94% |
Conditions
- Temperature
- 90 °C
Yield
- 77% of 2-[[2-[(1,3-dimethylpyrazol-4-yl)amino]-5-(trifluoromethyl)pyridin-4-yl]amino]-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 |
|---|---|---|---|---|---|---|
| N-(1,3-dimethylpyrazol-4-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine; 2-Amino-N-methylbenzamide | 1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine); Palladium (II) acetate | Cesium carbonate | 1,4-Dioxane | 90 °C | — | 77% (this run) |
| 2-[2-Chloro-5-(trifluoromethyl)pyridin-4-ylamino]-N-methylbenzamide; 1,3-dimethyl-1H-pyrazol-4-amine | (R)-(-)-1-[(S)-2-(Dicyclohexylphosphino)ferrocenyl]ethyldi-t-butylphosphine;Ferrocene, 1-[(1R)-1-[bis(1,1-dimethylethyl)phosphino]ethyl]-2-(dicyclohexylphosphino)-, (2R)-; Palladium (II) acetate | sodium 2-methylpropan-2-olate | 1,2-Dimethoxyethane | 150 °C | — | 34% |
Procedure
Copied from the source record, unedited
(9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (76 mg, 0.13 mmol) and diacetoxypalladium (14.77 mg, 0.07 mmol) were dissolved in dioxane (15 mL) and argon was let to bubble in the mixture for 5 minutes. 2-amino-N- methylbenzamide (336 mg, 2.24 mmol), N-(1,3-dimethyl-1H-pyrazol-4-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine (503 mg, 1.32 mmol) and cesium carbonate (858 mg, 2.63 mmol) were added and the reaction was heated to 90 °C, over a period of 90 minutes under nitrogen. LCMS didn't show a complete clean reaction (as Cs2CO3 got stuck on the flask). Vigourous stirring was applied and theaction was heated to 90 °C, over a period of 90 minutes under nitrogen. Crude LCMS was as expected. The reaction mixture was allowed to cool to room temperature under stirring, diluted with di
The source
This record comes from experimental reaction archive (ord-fc2357d340a54ad6a62277f1372b8047). Open the source and check it against what is on this page.
experimental reaction archive record ord-fc2357d340a54ad6a62277f1372b8047 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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