Buchwald–Hartwig amination: 8-Chloro-4-methyl-2-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine → N-(6-Methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)-4-methyl-2-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-8-amine
34% yield, run at 100 °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 | 8-Chloro-4-methyl-2-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine | C₁₁H₁₂ClF₃N₂O | |
| Reactant | 6-Methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-ylamine | C₁₀H₁₂N₄O | |
| Reagent | Cesium carbonate | CCs₂O₃ | |
| Catalyst | 2-(Dicyclohexylphosphino)biphenyl | C₂₄H₃₁P | |
| Catalyst | Palladium (II) acetate | C₄H₈O₄Pd | |
| Solvent | 1,2-Dimethoxyethane | C₄H₁₀O₂ | |
| Product | N-(6-Methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)-4-methyl-2-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-8-amine | C₂₁H₂₃F₃N₆O₂ | 33.89% |
Conditions
- Temperature
- 100 °C
Yield
- 34% of N-(6-Methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)-4-methyl-2-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-8-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 |
|---|---|---|---|---|---|
| Tris(1,1-dimethylethyl)phosphine; (1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladium | Cesium carbonate | 1,2-Dimethoxyethane | 100 °C | — | 85% |
| 2-(Dicyclohexylphosphino)biphenyl; Palladium (II) acetate | Cesium carbonate | 1,2-Dimethoxyethane | 100 °C | — | 34% (this run) |
Procedure
Copied from the source record, unedited
8-chloro-4-methyl-2-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (60 % purity, 314 mg, 0.67 mmol), 6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-amine (137 mg, 0.67 mmol), PALLADIUM(II) ACETATE (15.07 mg, 0.07 mmol), 2-(DICYCLOHEXYLPHOSPHINO)BIPHENYL (23.53 mg, 0.07 mmol) and Cs2CO3 (328 mg, 1.01 mmol) were placed in a microwave vial. The vial was capped and flushed with argon. DME (3 mL) was added via a syringe and the resulting mixture was heated to 100°C in a microwave apparatus for 2 h. The reaction mixture was diluted with dichloromethane, filtered and concentrated. The residue was purified first by column chromatography using Silica stationary phase and gradient elution with increasing concentration of methanol, from 0 to 8 %, in dichloromethane, and then by
The source
This record comes from experimental reaction archive (ord-f5f1be85a079463c9088e7a774cb07f5). Open the source and check it against what is on this page.
experimental reaction archive record ord-f5f1be85a079463c9088e7a774cb07f5 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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