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
0% yield, run at 120 °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 | sodium 2-methylpropan-2-olate | C₄H₉NaO | |
| Catalyst | Binap, (A+-)- | C₄₄H₃₂P₂ | |
| Catalyst | Bis(dibenzylideneacetone)palladium | C₅₁H₄₂O₃Pd₂ | |
| Solvent | Toluene | C₇H₈ | |
| 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 | 0% |
Conditions
- Temperature
- 120 °C
Yield
- 0% 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% |
| 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% (this run) |
| 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
The aim is optimization. (R)-2-chloro-6-methyl-8-phenyl-5,6,7,8-tetrahydropyrimido[5,4-f][1,4]oxazepine (29 mg, 0.11 mmol), 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline (21.38 mg, 0.11 mmol), Sodium tert-butoxide (15.16 mg, 0.16 mmol), rac-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (9.17 mg, 0.01 mmol) and Tris(dibenzylideneacetone)dipalladium(0) (6.74 mg, 7.36 µmol) were added to a microwave vial then toluene (1 mL) was added. The reaction mixture was flushed with nitrogen and the mixture was heated to 120°C for 45 min. Small amount of product was formed. Abandoned.
The source
This record comes from experimental reaction archive (ord-53ad2bbc851349aeae5fd4d95fae57a4). Open the source and check it against what is on this page.
experimental reaction archive record ord-53ad2bbc851349aeae5fd4d95fae57a4 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
More Buchwald–Hartwig amination records
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