Buchwald–Hartwig amination: 4-(4-Bromobenzyl)morpholine → 5-fluoro-4-[2-methyl-3-(oxan-4-yl)imidazol-4-yl]-N-[4-(morpholin-4-ylmethyl)phenyl]pyrimidin-2-amine
6% yield, run at 110 °C, as recorded by experimental reaction archive. The written procedure is below. One of 4 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 | 4-(4-Bromobenzyl)morpholine | C₁₁H₁₄BrNO | |
| Reactant | 5-fluoro-4-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-5-yl)pyrimidin-2-amine | C₁₃H₁₆FN₅O | |
| Reagent | Sodium 2-methylbutan-2-olate | C₅H₁₁NaO | |
| Catalyst | 1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) | C₃₉H₃₂OP₂ | |
| Catalyst | Bis(dibenzylideneacetone)palladium | C₅₁H₄₂O₃Pd₂ | |
| Solvent | Toluene | C₇H₈ | |
| Product | 5-fluoro-4-[2-methyl-3-(oxan-4-yl)imidazol-4-yl]-N-[4-(morpholin-4-ylmethyl)phenyl]pyrimidin-2-amine | C₂₄H₂₉FN₆O₂ | 6.31% |
Conditions
- Temperature
- 110 °C
Yield
- 6% of 5-fluoro-4-[2-methyl-3-(oxan-4-yl)imidazol-4-yl]-N-[4-(morpholin-4-ylmethyl)phenyl]pyrimidin-2-amine.
Every recorded run making this product
4 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.
| Catalyst | Reagents | Solvent | Temp. | Time | Yield |
|---|---|---|---|---|---|
| 1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine); Bis(dibenzylideneacetone)palladium | Cesium carbonate | 1,4-Dioxane | 100 °C | — | 86% |
| 1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine); Bis(dibenzylideneacetone)palladium | Sodium 2-methylbutan-2-olate | Toluene | 110 °C | — | 6% (this run) |
| 2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl; Bis(dibenzylideneacetone)palladium | Sodium 2-methylbutan-2-olate | Butyl Acetate | 100 °C | — | 0% |
| (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-methylbutan-2-olate | 1,2-Dimethoxyethane | 90 °C | — | 0% |
Procedure
Copied from the source record, unedited
Tris(dibenzylideneacetone)dipalladium(0) (1.703 g, 1.86 mmol) and 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (2.58 g, 4.46 mmol) were dissolved in toluene (50 ml) in a 500 mL two-necked round-bottomed flask equipped with a condensor and activated at 50 °C for 40 min under argon. 5-fluoro-4-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-5-yl)pyrimidin-2-amine (12.84 g, 46.30 mmol), 4-(4-bromobenzyl)morpholine (13.64 g, 53.25 mmol), Sodium tert-pentoxide (8.16 g, 74.09 mmol) and extra toluene (250 mL) were added. The total volume of the reaction mixture was deoxygenized carefully by switching vacuum-argon 10-times and heated to 110 °C under argon. After 10 min the mixture turned into green. The reaction was monitored by HPLC, after 22 h only ca 65 %. The reactuion was stopped and t
The source
This record comes from experimental reaction archive (ord-834b5e1dd58a47728397e6966452dba7). Open the source and check it against what is on this page.
experimental reaction archive record ord-834b5e1dd58a47728397e6966452dba7 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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