Buchwald–Hartwig amination: (2R)-8-chloro-4-methyl-2-phenyl-3,5-dihydro-2H-pyrido[3,2-f][1,4]oxazepine → gamma-Secretase modulator 6
101% yield, run at 120 °C, as recorded by experimental reaction archive. The written procedure is below. One of 3 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 | (2R)-8-chloro-4-methyl-2-phenyl-3,5-dihydro-2H-pyrido[3,2-f][1,4]oxazepine | C₁₅H₁₅ClN₂O | |
| Reactant | 6-Methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-ylamine | C₁₀H₁₂N₄O | |
| Reagent | Potassium Carbonate | CK₂O₃ | |
| Catalyst | Binap, (A+-)- | C₄₄H₃₂P₂ | |
| Catalyst | Palladium (II) acetate | C₄H₈O₄Pd | |
| Solvent | Toluene | C₇H₈ | |
| Product | gamma-Secretase modulator 6 | C₂₅H₂₆N₆O₂ | 100.61% |
Conditions
- Temperature
- 120 °C
Yield
- 101% of gamma-Secretase modulator 6.
Every recorded run making this product
3 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 |
|---|---|---|---|---|---|
| Binap, (A+-)-; Palladium (II) acetate | Potassium Carbonate | Toluene | 120 °C | — | 101% (this run) |
| Binap, (A+-)-; Bis(dibenzylideneacetone)palladium | sodium 2-methylpropan-2-olate | Toluene | 100 °C | — | 32% |
| Tris(1,1-dimethylethyl)phosphine; Bis(dibenzylideneacetone)palladium | Cesium carbonate | 120 °C | — | 0% |
Procedure
Copied from the source record, unedited
Charged a round-bottom flask with a mixture of 6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-amine (5.0 g, 24.48 mmol), (R)-8-chloro-4-methyl-2-phenyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (6.73 g, 24.48 mmol), palladium (II) acetate (0.165 g, 0.73 mmol), rac-BINAP (0.762 g, 1.22 mmol), potassium carbonate (5.08 g, 36.72 mmol), and toluene (100 mL). The atmosphere was inerted through consecutive vacuum-nitrogen purge cycles, then heated at 120 °C for 16 hours. HPLC-UV shows a small percentage (<5%) of starting materials remaining. Heating was continued for another 2 hours, then the heating block was removed and the mixture was allowed to cool to room temperature. Added 200 mL dichloromethane and adjusted the pH to 2 with 2.0N aqueous HCl. Separated the phases and basified the aq
The source
This record comes from experimental reaction archive (ord-0624d5800c4b4df5ab74722e43784236). Open the source and check it against what is on this page.
experimental reaction archive record ord-0624d5800c4b4df5ab74722e43784236 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.
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