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
32% yield, run at 100 °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 | sodium 2-methylpropan-2-olate | C₄H₉NaO | |
| Catalyst | Binap, (A+-)- | C₄₄H₃₂P₂ | |
| Catalyst | Bis(dibenzylideneacetone)palladium | C₅₁H₄₂O₃Pd₂ | |
| Solvent | Toluene | C₇H₈ | |
| Product | gamma-Secretase modulator 6 | C₂₅H₂₆N₆O₂ | 32.29% |
Conditions
- Temperature
- 100 °C
Yield
- 32% 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% |
| Binap, (A+-)-; Bis(dibenzylideneacetone)palladium | sodium 2-methylpropan-2-olate | Toluene | 100 °C | — | 32% (this run) |
| Tris(1,1-dimethylethyl)phosphine; Bis(dibenzylideneacetone)palladium | Cesium carbonate | 120 °C | — | 0% |
Procedure
Copied from the source record, unedited
6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-amine (558 mg, 2.73 mmol), (R)-8-chloro-4-methyl-2-phenyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (750 mg, 2.73 mmol), Sodium tert-butoxide (394 mg, 4.09 mmol), rac-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (119 mg, 0.19 mmol) and Tris(dibenzylideneacetone)dipalladium(0) (175 mg, 0.19 mmol) were added to a microwave vial followed by toluene (11 mL). The reaction mixture was flushed with nitrogen and the mixture was heated to 100°C and stirred overnight. The reaction was complete. The solids were filtered off and washed with ethyl acetate. The organic solution was extracted by sat NaHCO3 solution. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The crude product was purified by column chromatograph
The source
This record comes from experimental reaction archive (ord-bea3ac5058c048368377611c2ed94139). Open the source and check it against what is on this page.
experimental reaction archive record ord-bea3ac5058c048368377611c2ed94139 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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