Buchwald–Hartwig amination, record ord-180ffbd2722940d2bf70ecaf0fc8e2ac
One recorded run of this reaction. Below is what the source recorded, and nothing added to it.
What was in the flask
| Role | Species | Formula | Yield |
|---|---|---|---|
| Reactant | 3-(2-Chloro-5-fluoro-4-pyridinyl)-5,5-dimethyl-4,6-dihydropyrrolo[2,1-e]pyrazole | C₁₃H₁₃ClFN₃ | |
| Reactant | Tert-butyl cis-(3-carbamoylcyclohexyl)carbamate | C₁₂H₂₂N₂O₃ | |
| Reagent | Cesium carbonate | CCs₂O₃ | |
| Catalyst | 1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) | C₃₉H₃₂OP₂ | |
| Catalyst | Tetrakis(triphenylphosphine)palladium | C₇₂H₆₀P₄Pd | |
| Solvent | 1,4-Dioxane | C₄H₈O₂ | |
| Product | tert-butyl N-[(1R,3S)-3-[[4-(5,5-dimethyl-4,6-dihydropyrrolo[2,1-e]pyrazol-3-yl)-5-fluoro-2-pyridinyl]carbamoyl]cyclohexyl]carbamate | C₂₅H₃₄FN₅O₃ | 53.6% |
Conditions
- Temperature
- 120 °C
Yield
- 54% of tert-butyl N-[(1R,3S)-3-[[4-(5,5-dimethyl-4,6-dihydropyrrolo[2,1-e]pyrazol-3-yl)-5-fluoro-2-pyridinyl]carbamoyl]cyclohexyl]carbamate.
Procedure
Copied from the source record, unedited
Tetrakis(triphenylphosphine)palladium(0) (159 mg, 0.14 mmol) was added to 3-(2-chloro-5-fluoropyridin-4-yl)-5,5-dimethyl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole (365.4 mg, 1.38 mmol), tert-butyl ((1R,3S)-3-carbamoylcyclohexyl)carbamate (333 mg, 1.38 mmol) and 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (Xantphos) (159 mg, 0.28 mmol)and Cesium carbonate (1344 mg, 4.13 mmol) in 1,4-dioxane (15 mL). The resulting suspension was degassed for 10 minutes under nitrogen and then stirred at 120 °C for 8 hours overnight in the microwave reactor. The reaction mixture was partioned between water (30 mL) and DCM (15 mL) and seperated. _LCMS analysis showed product in the aqueous extract._ The aqueous layer was extracted with DCM (2 X 20 mL). LCMS analysis showed some product still within in the
The source
This record comes from experimental reaction archive (ord-180ffbd2722940d2bf70ecaf0fc8e2ac). Open the source and check it against what is on this page.
experimental reaction archive record ord-180ffbd2722940d2bf70ecaf0fc8e2ac 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.