Buchwald–Hartwig amination: 2-[2-Chloro-5-(trifluoromethyl)pyridin-4-ylamino]-N-methylbenzamide → 2-[[2-[(1,3-dimethylpyrazol-4-yl)amino]-5-(trifluoromethyl)pyridin-4-yl]amino]-N-methylbenzamide
34% yield, run at 150 °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 | 2-[2-Chloro-5-(trifluoromethyl)pyridin-4-ylamino]-N-methylbenzamide | C₁₄H₁₁ClF₃N₃O | |
| Reactant | 1,3-dimethyl-1H-pyrazol-4-amine | C₅H₉N₃ | |
| Reagent | sodium 2-methylpropan-2-olate | C₄H₉NaO | |
| Catalyst | (R)-(-)-1-[(S)-2-(Dicyclohexylphosphino)ferrocenyl]ethyldi-t-butylphosphine;Ferrocene, 1-[(1R)-1-[bis(1,1-dimethylethyl)phosphino]ethyl]-2-(dicyclohexylphosphino)-, (2R)- | C₃₂H₆₂FeP₂ | |
| Catalyst | Palladium (II) acetate | C₄H₈O₄Pd | |
| Solvent | 1,2-Dimethoxyethane | C₄H₁₀O₂ | |
| Product | 2-[[2-[(1,3-dimethylpyrazol-4-yl)amino]-5-(trifluoromethyl)pyridin-4-yl]amino]-N-methylbenzamide | C₁₉H₁₉F₃N₆O | 33.67% |
Conditions
- Temperature
- 150 °C
Yield
- 34% 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% |
| 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% (this run) |
Procedure
Copied from the source record, unedited
Palladium(II) acetate (8.17 mg, 0.04 mmol), (R)-(-)-1-[(S)-2-(Dicyclohexylphosphino)ferrocenyl]ethyldi-t-butylphosphine (20.40 mg, 0.04 mmol), Sodium tert-butoxide (0.052 mL, 0.42 mmol), 1,3-dimethyl-1H-pyrazol-4-amine (40.5 mg, 0.36 mmol) and 2-(2-chloro-5-(trifluoromethyl)pyridin-4-ylamino)-N-methylbenzamide (100 mg, 0.30 mmol) were suspended in DME (2.5 mL) and sealed into a microwave tube. The reaction was heated to 150 °C for 30 minutes in the microwave reactor and cooled to RT. The crude product was purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 7M NH3/MeOH and pure fractions were evaporated to dryness to afford 2-(2-(1,3-dimethyl-1H-pyrazol-4-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)-N-methylbenzamide (41.3 mg,
The source
This record comes from experimental reaction archive (ord-2cb0b90157da471ebcc18c85cfe6adf7). Open the source and check it against what is on this page.
experimental reaction archive record ord-2cb0b90157da471ebcc18c85cfe6adf7 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.
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