Buchwald–Hartwig amination: Benzene, 1-iodo-3-(trifluoromethyl)- → 5-bromo-4-methoxy-N-[3-(trifluoromethyl)phenyl]pyrimidin-2-amine
43% 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 | Benzene, 1-iodo-3-(trifluoromethyl)- | C₇H₄F₃I | |
| Reactant | 2-Amino-5-bromo-4-methoxypyrimidine | C₅H₆BrN₃O | |
| 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 | Toluene | C₇H₈ | |
| Product | 5-bromo-4-methoxy-N-[3-(trifluoromethyl)phenyl]pyrimidin-2-amine | C₁₂H₉BrF₃N₃O | 43.23% |
Conditions
- Temperature
- 90 °C
Yield
- 43% of 5-bromo-4-methoxy-N-[3-(trifluoromethyl)phenyl]pyrimidin-2-amine.
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.
| Catalyst | Reagents | Solvent | Temp. | Time | Yield |
|---|---|---|---|---|---|
| 1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine); Palladium (II) acetate | Cesium carbonate | Toluene | 90 °C | — | 43% (this run) |
| Binap, (A+-)-; Palladium (II) acetate | Cesium carbonate | Toluene | 80 °C | — | 9% |
Procedure
Copied from the source record, unedited
repeat of _EN06995-58\Reaction_ but using Xantphos **_Aim:-_ prepare target for further use.** 1-iodo-3-(trifluoromethyl)benzene (0.171 ml, 1.19 mmol), 5-bromo-4-methoxypyrimidin-2-amine (0.202 g, 0.99 mmol), PALLADIUM(II) ACETATE (0.011 g, 0.05 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) - Xantphos (0.029 g, 0.05 mmol) and cesium carbonate (0.387 g, 1.19 mmol) were mixed in toluene (5ml), purged with nitrogen and stirred in a sealed tube at 90 °C overnight. LCMS: pH = 3, 2 minute run time, shows sign of product at Rt = 1.41 min The reaction mixture was diluted with EtOAc (20 ml), filtered through a celite pad and concentrated to give 477 mg yellow solid. TLC (1:1 - EtOAc : n-heptane) see diagram UV only This was disolved in DCM, absorbed onto a samplet and purif
The source
This record comes from experimental reaction archive (ord-1f9578b402a0413a8d3c28c86e02d21e). Open the source and check it against what is on this page.
experimental reaction archive record ord-1f9578b402a0413a8d3c28c86e02d21e 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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