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
30% yield, run at 130 °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 | 1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) | C₃₉H₃₂OP₂ | |
| Catalyst | Palladium (II) acetate | C₄H₈O₄Pd | |
| Solvent | 1,4-Dioxane | C₄H₈O₂ | |
| 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 | 30.38% |
Conditions
- Temperature
- 130 °C
Yield
- 30% 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% (this run) |
| 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% |
| 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
(R)-2-chloro-6-methyl-8-phenyl-5,6,7,8-tetrahydropyrimido[5,4-f][1,4]oxazepine (400 mg, 1.45 mmol), 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline (265 mg, 1.31 mmol), Cesium carbonate (709 mg, 2.18 mmol), Palladium(II) acetate (32.6 mg, 0.15 mmol) and 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (168 mg, 0.29 mmol) were added to a microwave vial then dioxane (18 mL) was added. The reaction mixture was flushed with argon and then heated at 140°C for 60 min in a MW. The reaction mixture was filtered through celite and concentrated. The crude product was purified by silica flash chromatography using a gradient of methanol (0 to 5%) in dichloromethane. Not pure enough. The product was purified further with preparative chromatography. The productcontainíng product was collected and the meth
The source
This record comes from experimental reaction archive (ord-8ae4472e49574adcac504920ccdd2d20). Open the source and check it against what is on this page.
experimental reaction archive record ord-8ae4472e49574adcac504920ccdd2d20 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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