Buchwald–Hartwig amination: N-(5-Bromopyrazin-2-YL)acetamide → N-[5-(4-methylpiperazin-1-yl)pyrazin-2-yl]acetamide
80% 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 | N-(5-Bromopyrazin-2-YL)acetamide | C₆H₆BrN₃O | |
| Reactant | 1-Methylpiperazine | C₅H₁₂N₂ | |
| Reagent | potassium 2-methylpropan-2-olate | C₄H₉KO | |
| Catalyst | Tris(1,1-dimethylethyl)phosphine | C₁₂H₂₇P | |
| Catalyst | Bis(dibenzylideneacetone)palladium | C₅₁H₄₂O₃Pd₂ | |
| Solvent | Dimethylformamide | C₃H₇NO | |
| Product | N-[5-(4-methylpiperazin-1-yl)pyrazin-2-yl]acetamide | C₁₁H₁₇N₅O | 79.51% |
Conditions
- Temperature
- 120 °C
Yield
- 80% of N-[5-(4-methylpiperazin-1-yl)pyrazin-2-yl]acetamide.
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.
- Methyl 3-(4-methyl-1-piperazinyl)-5-nitrobenzoate65%
- Methyl 4-((3-(4-methylpiperazin-1-yl)pyridin-2-yl)methoxy)benzoate64%
- 1-(4-Chloro-2-methoxyphenyl)-4-methylpiperazine64%
- 4-(4-Methyl-1-piperazinyl)phenol51%
- 1-(5-Bromopyridin-3-yl)-4-methylpiperazine21%
- 1-(3-bromo-1-methyl-1H-1,2,4-triazol-5-yl)-4-methylpiperazine0%
- Ethyl 4-[(2,4-dichlorophenyl)amino]-7-methoxy-6-(4-methylpiperazin-1-yl)quinoline-3-carboxylate0%
- Ethyl 4-[(2,4-difluorophenyl)amino]-6-(4-methylpiperazin-1-yl)quinoline-3-carboxylate0%
- N-[5-(1H-imidazol-2-yl)-2-methylphenyl]-4-[[3-(4-methylpiperazin-1-yl)-2-pyridinyl]methoxy]benzamide0%
- 1-(4-Chloro-2-methoxyphenyl)-4-methylpiperazine0%
Procedure
Copied from the source record, unedited
1-methylpiperazine (2.318 g, 23.14 mmol), N-(5-bromopyrazin-2-yl)acetamide (1 g, 4.63 mmol), tri-tert-butylphosphine (1.873 g, 9.26 mmol), tris(dibenzylideneacetone)dipalladium (0.085 g, 0.09 mmol) and potassium 2-methylpropan-2-olate (1.039 g, 9.26 mmol) were suspended in DMF (9.26 ml) and sealed into a microwave tube. The reaction was heated to 120 °C for 40 minutes in the microwave reactor and cooled to RT. The mixture was diluted with methanol and acidified with HCl, then the solution was purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 7M NH3/MeOH and pure fractions were evaporated to dryness to afford N-(5-(4-methylpiperazin-1-yl)pyrazin-2-yl)acetamide (0.866 g, 80 %) as a dark oil. Used without further purification.
The source
This record comes from experimental reaction archive (ord-96727602adb24b28af9c737e24f7315c). Open the source and check it against what is on this page.
experimental reaction archive record ord-96727602adb24b28af9c737e24f7315c 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.
The pathway is a separate question, kept on separate pages. A mechanism here is the canonical arrow pushing for a class, run on real structures and labelled rule-derived. It is not evidence, and this record is not a mechanism.
Where to next
More Buchwald–Hartwig amination records
Other runs of this class, one page per distinct transformation.
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