Buchwald–Hartwig amination: 2-(2-Chloro-5-(trifluoromethyl)pyridin-4-ylamino)-6-methoxy-N-methylbenzamide → 2-(2-(1,3-dimethyl-1H-pyrazol-5-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)-6-methoxy-N-methylbenzamide
44% 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 | 2-(2-Chloro-5-(trifluoromethyl)pyridin-4-ylamino)-6-methoxy-N-methylbenzamide | C₁₅H₁₃ClF₃N₃O₂ | |
| Reactant | 1,3-Dimethyl-1H-pyrazol-5-amine | C₅H₉N₃ | |
| 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-dimethyl-1H-pyrazol-5-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)-6-methoxy-N-methylbenzamide | C₂₀H₂₁F₃N₆O₂ | 44% |
Conditions
- Temperature
- 90 °C
Yield
- 44% of 2-(2-(1,3-dimethyl-1H-pyrazol-5-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)-6-methoxy-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 |
|---|---|---|---|---|---|---|
| 2-(2-Chloro-5-(trifluoromethyl)pyridin-4-ylamino)-6-methoxy-N-methylbenzamide; 1,3-Dimethyl-1H-pyrazol-5-amine | 1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine); Palladium (II) acetate | Cesium carbonate | 1,4-Dioxane | 90 °C | — | 44% (this run) |
| N-(1,3-dimethylpyrazol-5-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine; 2-amino-6-methoxy-N-methylbenzamide | 1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine); Palladium (II) acetate | Cesium carbonate | 1,4-Dioxane | 95 °C | — | 42% |
Procedure
Copied from the source record, unedited
_2-(2-chloro-5-(trifluoromethyl)pyridin-4-ylamino)-6-methoxy-N-methylbenzamide (1.66 g, 4.61 mmol)_ _,_ _1,3-dimethyl-1H-pyrazol-5-amine (0.523 g, 4.71 mmol)_ _,_ _diacetoxypalladium (0.083 g, 0.37 mmol)_ _,_ _(9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.427 g, 0.74 mmol)_ _and_ _cesium carbonate (1.804 g, 5.54 mmol)_ _were mixed together in_ _dioxane (30 mL)_ _. Reaction was degassed with argon and was stirred at_ _90 °C_ _for 3 hours under argon.The mixture was filtered ,the filtrate was concentrated and purified by flash chromatography on silica gel 15-40µm eluting with __0_ _to_ _4_ _% methanol in CH2Cl2/AcOEt (60/40).The product obtained was not enough pure so the product was repurified by flash chromatography on silica gel 15-40µm eluting with 0 to 4% methanol in CH
The source
This record comes from experimental reaction archive (ord-ffcc436f225c440ca5c8c1a40df255a3). Open the source and check it against what is on this page.
experimental reaction archive record ord-ffcc436f225c440ca5c8c1a40df255a3 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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