Buchwald–Hartwig amination: 4-(4-Chloro-3-fluorobenzyl)morpholine → 5-Fluoro-N-(2-fluoro-4-(morpholinomethyl)phenyl)-4-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-5-yl)pyrimidin-2-amine
11% yield, run at 102 °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 | 4-(4-Chloro-3-fluorobenzyl)morpholine | C₁₁H₁₃ClFNO | |
| Reactant | 5-fluoro-4-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-5-yl)pyrimidin-2-amine | C₁₃H₁₆FN₅O | |
| Reagent | potassium 2-methylpropan-2-olate | C₄H₉KO | |
| Catalyst | 2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl | C₃₃H₄₉P | |
| Catalyst | Bis(dibenzylideneacetone)palladium | C₅₁H₄₂O₃Pd₂ | |
| Solvent | 1,4-Dioxane | C₄H₈O₂ | |
| Product | 5-Fluoro-N-(2-fluoro-4-(morpholinomethyl)phenyl)-4-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-5-yl)pyrimidin-2-amine | C₂₄H₂₈F₂N₆O₂ | 11.43% |
Conditions
- Temperature
- 102 °C
Yield
- 11% of 5-Fluoro-N-(2-fluoro-4-(morpholinomethyl)phenyl)-4-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-5-yl)pyrimidin-2-amine.
Procedure
Copied from the source record, unedited
To degassed 1,4-dioxane (39.2 ml) in a flame-dried and argonflushed 250 mL roundbottomed flask were added 5-fluoro-4-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-5-yl)pyrimidin-2-amine (1.076 g, 3.88 mmol) and 4-(4-chloro-3-fluorobenzyl)morpholine (0.9 g, 3.92 mmol) followed by POTASSIUM TERT-BUTOXIDE (0.572 g, 5.09 mmol) whilst stirring. The resulting slurry was flushed with argon and stirred for 5-10 minutes followed by addition of TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (0.359 g, 0.39 mmol) and 2-Dicyclohexylphosphino-2',4',6'-tri-iso- propyl-1,1'-biphenyl (0.374 g, 0.78 mmol), whereafter the reaction mixture was flushed with argon again and heated to 102 °C and stirred under argon for 3 h. No further conversion occurred after 2 hours. The completion of the reaction was controll
The source
This record comes from experimental reaction archive (ord-68a2d19644de420ea283722f281ee146). Open the source and check it against what is on this page.
experimental reaction archive record ord-68a2d19644de420ea283722f281ee146 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
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