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
102% yield, run at 120 °C, as recorded by experimental reaction archive. The written procedure is 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 | 101.53% |
Conditions
- Temperature
- 120 °C
Yield
- 102% of gamma-Secretase modulator 6.
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 (4.5 g, 22.03 mmol), (R)-8-chloro-4-methyl-2-phenyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (6.05 g, 22.03 mmol), palladium (II) acetate (0.148 g, 0.66 mmol), rac-BINAP (0.686 g, 1.10 mmol), potassium carbonate (4.57 g, 33.05 mmol), and toluene (90 mL). The atmosphere s inerted through itrogen purge cycles, then heated at 120 °C or 16 hours. HPLC-UV shows <5% of starting materials remaining. The heating block was removed and the mixture was allowed to cool to room temperature. Added 300 mL dichloromethane and adjusted the pH to 2 with 2.0N aqueous HCl. Separated the phases and basified the aqueous with 1.0N aqueous sodium hydroxide. Extracted with 200 mL DCM, followed by a second ext
The source
This record comes from experimental reaction archive (ord-b30e73dcf3ae428d887dca581acb0b4f). Open the source and check it against what is on this page.
experimental reaction archive record ord-b30e73dcf3ae428d887dca581acb0b4f 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
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