Buchwald–Hartwig amination: 2,5-Dichloro-4-iodopyridine → 8-[(2,5-Dichloropyridin-4-yl)amino]-2-methyl-3,4-dihydroisoquinolin-1-one
43% yield, run at 100 °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 | 2,5-Dichloro-4-iodopyridine | C₅H₂Cl₂IN | |
| Reactant | 8-amino-2-methyl-3,4-dihydroisoquinolin-1(2H)-one | C₁₀H₁₂N₂O | |
| 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 | 8-[(2,5-Dichloropyridin-4-yl)amino]-2-methyl-3,4-dihydroisoquinolin-1-one | C₁₅H₁₃Cl₂N₃O | 42.5% |
Conditions
- Temperature
- 100 °C
Yield
- 43% of 8-[(2,5-Dichloropyridin-4-yl)amino]-2-methyl-3,4-dihydroisoquinolin-1-one.
Other recorded runs with the same starting material
No other run in the library makes this product. These runs of the same class start from one of the same reactants, which is the nearest company this record has.
- 2-[(2,5-dichloro-4-pyridinyl)amino]-N-(methyloxy)benzamide69%
- 2-(2,5-dichloropyridin-4-ylamino)-4-fluoro-N-methylbenzamide35%
- 8-[[2-[(1,3-Dimethylpyrazol-4-yl)amino]-5-(trifluoromethyl)-4-pyridyl]amino]-2-methyl-3,4-dihydroisoquinolin-1-one34%
- 2-[(2,5-Dichloro-4-pyridinyl)amino]-N-methylbenzamide32%
- 2-(2,5-dichloropyridin-4-ylamino)-5-fluoro-N-methylbenzamide13%
- 6-[(1,3-Dimethylpyrazol-4-yl)amino]-4-[(2-methyl-1-oxo-3,4-dihydroisoquinolin-8-yl)amino]pyridine-3-carbonitrile33%
Procedure
Copied from the source record, unedited
diacetoxypalladium (0.205 g, 0.91 mmol) was added to a stirred suspension of 2,5-dichloro-4-iodopyridine (5 g, 18.26 mmol), 8-amino-2-methyl-3,4-dihydroisoquinolin-1(2H)-one (3.22 g, 18.26 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (1.056 g, 1.83 mmol) and cesium carbonate (8.92 g, 27.38 mmol) dissolved in 1,4-dioxane (100 mL). The resulting suspension was degassed (3 times) with nitrogen and was stirred at 100°C for 16 hours. The reaction mixture was allowed to cool to room temperature, diluted with DCM (100 mL) and filtered. The residue was washed with DCM. The filtrates was combined evaporated to dryness. The crude product was purified by flash chromatography on silica gel eluting with 0 to 10% ethyl acetate in dichloromethane. The solvent was evaporated to dryness
The source
This record comes from experimental reaction archive (ord-bc24f3de1ac64e7e96966f7efd955e5c). Open the source and check it against what is on this page.
experimental reaction archive record ord-bc24f3de1ac64e7e96966f7efd955e5c 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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