Buchwald–Hartwig amination: 4-(6-Chloro-5-methyl-pyrimidin-4-yloxy)-piperidine-1-carboxylic acid isopropyl ester → 4-[6-(6-Methanesulfonyl-2-methyl-pyridin-3-ylamino)-5-methyl-pyrimidin-4-yloxy]-piperidine-1-carboxylic Acid Isopropyl Ester
54% yield, run at 90 °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 | 4-(6-Chloro-5-methyl-pyrimidin-4-yloxy)-piperidine-1-carboxylic acid isopropyl ester | C₁₄H₂₀ClN₃O₃ | |
| Reactant | 2-Methyl-6-(methylsulfonyl)pyridin-3-amine | C₇H₁₀N₂O₂S | |
| Reagent | sodium 2-methylpropan-2-olate | C₄H₉NaO | |
| Catalyst | 2,8,9-Triisobutyl-2,5,8,9-tetraaza-1-phosphabicyclo(3.3.3)undecane | C₁₈H₃₉N₄P | |
| Catalyst | Palladium (II) acetate | C₄H₈O₄Pd | |
| Solvent | 1,4-Dioxane | C₄H₈O₂ | |
| Product | 4-[6-(6-Methanesulfonyl-2-methyl-pyridin-3-ylamino)-5-methyl-pyrimidin-4-yloxy]-piperidine-1-carboxylic Acid Isopropyl Ester | C₂₁H₂₉N₅O₅S | 54.09% |
Conditions
- Temperature
- 90 °C
Yield
- 54% of 4-[6-(6-Methanesulfonyl-2-methyl-pyridin-3-ylamino)-5-methyl-pyrimidin-4-yloxy]-piperidine-1-carboxylic Acid Isopropyl Ester.
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.
Procedure
Copied from the source record, unedited
Sodium tert-butoxide (9.83 mL, 80.31 mmol) was added portionwise to isopropyl 4-(6-chloro-5-methylpyrimidin-4-yloxy)piperidine-1-carboxylate (10.50 g, 33.46 mmol) and 2-methyl-6-(methylsulfonyl)pyridin-3-amine (5.92 g, 31.79 mmol) in dioxane (160 mL) at 18ºC over a period of 1 minute under nitrogen. The reaction was degassed with vacuum / nitrogen (6 times) and 2,8,9-Triisobutyl-2,5,8,9-tetraaza-1-phosphabicyclo{3.3.3}undecane (0.238 mL, 0.67 mmol) and Palladium(II) acetate (0.075 g, 0.33 mmol) was added and the suspension was stirred at 90 °C for a further 2 hours. More 2,8,9-Triisobutyl-2,5,8,9-tetraaza-1-phosphabicyclo{3.3.3}undecane (0.238 mL, 0.67 mmol) and Palladium(II) acetate (0.075 g, 0.33 mmol) was added and the suspension was stirred at 90 °C for a further another 2 hours before
The source
This record comes from experimental reaction archive (ord-3c40e6ac0b7c4653beac4f187a4bcda3). Open the source and check it against what is on this page.
experimental reaction archive record ord-3c40e6ac0b7c4653beac4f187a4bcda3 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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