Buchwald–Hartwig amination: (R)-2-chloro-6-methyl-8-phenyl-5,6,7,8-tetrahydropyrimido[5,4-f][1,4]oxazepine → (R)-N-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)-6-methyl-8-phenyl-5,6,7,8-tetrahydropyrimido[5,4-f][1,4]oxazepin-2-amine
7% yield, run at 100 °C, as recorded by experimental reaction archive. The written procedure is below. One of 7 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 | (R)-2-chloro-6-methyl-8-phenyl-5,6,7,8-tetrahydropyrimido[5,4-f][1,4]oxazepine | C₁₄H₁₄ClN₃O | |
| Reactant | 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline | C₁₁H₁₃N₃O | |
| Reagent | Cesium carbonate | CCs₂O₃ | |
| Catalyst | 2-(Dicyclohexylphosphino)biphenyl | C₂₄H₃₁P | |
| Catalyst | Palladium (II) acetate | C₄H₈O₄Pd | |
| Solvent | 1,2-Dimethoxyethane | C₄H₁₀O₂ | |
| Product | (R)-N-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)-6-methyl-8-phenyl-5,6,7,8-tetrahydropyrimido[5,4-f][1,4]oxazepin-2-amine | C₂₅H₂₆N₆O₂ | 6.84% |
Conditions
- Temperature
- 100 °C
Yield
- 7% of (R)-N-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)-6-methyl-8-phenyl-5,6,7,8-tetrahydropyrimido[5,4-f][1,4]oxazepin-2-amine.
Every recorded run making this product
7 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 | 1,4-Dioxane | 130 °C | — | 30% |
| Tris(1,1-dimethylethyl)phosphine; Palladium (II) acetate | Cesium carbonate | 1,4-Dioxane | 120 °C | — | 15% |
| 2-(Dicyclohexylphosphino)biphenyl; Palladium (II) acetate | Cesium carbonate | 1,2-Dimethoxyethane | 100 °C | — | 7% (this run) |
| Binap, (A+-)-; Palladium (II) acetate | Potassium Carbonate | Toluene | 120 °C | — | 0% |
| Tris(1,1-dimethylethyl)phosphine; Palladium (II) acetate | Sodium 2-methylbutan-2-olate | 1,4-Dioxane | 120 °C | — | 0% |
| Binap, (A+-)-; Bis(dibenzylideneacetone)palladium | sodium 2-methylpropan-2-olate | Toluene | 120 °C | — | 0% |
| 1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine); Bis(dibenzylideneacetone)palladium | Cesium carbonate | 1,4-Dioxane | 130 °C | — | 0% |
Procedure
Copied from the source record, unedited
Palladium(II) acetate (6.68 mg, 0.03 mmol), 2-(Dicyclohexylphosphino)biphenyl (10.42 mg, 0.03 mmol) and Cesium carbonate (0.388 g, 1.19 mmol) were put in a 5 mL microwave vial and sealed. The vial was flushed with argon. (R)-2-chloro-6-methyl-8-phenyl-5,6,7,8-tetrahydropyrimido[5,4-f][1,4]oxazepine (0.082 g, 0.30 mmol) in DME (5 mL) was added to the vial. The reaction mixture was run in the microwave at 100°C for 60 minutes. Forgot the aniline! Added 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline (0.086 g, 0.36 mmol) and a small spatula of Palladium(II) acetate and 2-(Dicyclohexylphosphino)biphenyl and the reaction mixture was run in the microwave for 60 minutes for 100°C. The reaction mixture was filtrated through celite, concentrated and purified first by preparative chromatography. The
The source
This record comes from experimental reaction archive (ord-5df7b290b65549a1949a950ac953d2d5). Open the source and check it against what is on this page.
experimental reaction archive record ord-5df7b290b65549a1949a950ac953d2d5 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.
Where to next
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