Buchwald–Hartwig amination: 3,5-Dibromopyridine → 1-(5-Bromopyridin-3-yl)-4-methylpiperazine
21% yield, run at 140 °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 | 3,5-Dibromopyridine | C₅H₃Br₂N | |
| Reactant | 1-Methylpiperazine | C₅H₁₂N₂ | |
| Reagent | sodium 2-methylpropan-2-olate | C₄H₉NaO | |
| Catalyst | 1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) | C₃₉H₃₂OP₂ | |
| Catalyst | Bis(dibenzylideneacetone)palladium | C₅₁H₄₂O₃Pd₂ | |
| Solvent | Toluene | C₇H₈ | |
| Product | 1-(5-Bromopyridin-3-yl)-4-methylpiperazine | C₁₀H₁₄BrN₃ | 21.27% |
Conditions
- Temperature
- 140 °C
Yield
- 21% of 1-(5-Bromopyridin-3-yl)-4-methylpiperazine.
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.
- N-[5-(4-methylpiperazin-1-yl)pyrazin-2-yl]acetamide80%
- 5-bromo-N-(2-methoxyethyl)-N-methylpyridin-3-amine68%
- 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%
- 3-bromo-5-[(3R)-3-methoxypyrrolidin-1-yl]pyridine51%
- 4-(4-Methyl-1-piperazinyl)phenol51%
- 4-(5-Bromopyridin-3-yl)morpholine50%
- 1-[4-(5-Bromo-3-pyridinyl)piperazin-1-yl]ethanone32%
- 5-bromo-N-(4-fluorophenyl)-N-methylpyridin-3-amine12%
- 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%
Procedure
Copied from the source record, unedited
Trial # 3: 3,5-dibromopyridine (1000 mg, 4.22 mmol), 1-methylpiperazine (423 mg, 4.22 mmol), Pd2(dba)3 (387 mg, 0.42 mmol), XANTPHOS (366 mg, 0.63 mmol), SODIUM TERT-BUTOXIDE (609 mg, 6.33 mmol), PhCH3 (10 mL) as added to a 10 mL microwave vial. This was degassed and refilled with N2 and then heated at 140 °C in microwave for 1h. LCMS showed reaction done with the peak at Rf0.52 showed a fragment mass of 256. Evaporated solvent. Residue purified by (CH3CN/H2O 0-30%+TFA buffer )to get the desired product 1-(5-bromopyridin-3-yl)-4-methylpiperazine (107 mg, 9.90 %). Trial # 1 3,5-dibromopyridine (1000 mg, 4.22 mmol), 1-methylpiperazine (423 mg, 4.22 mmol), Pd2(dba)3 (387 mg, 0.42 mmol), XANTPHOS (366 mg, 0.63 mmol), [Reactants], PhCH3 (5 mL) as added to a 10 mL microwave vial. This was
The source
This record comes from experimental reaction archive (ord-1cf3f1a64d944eabb1ba184483ae76fd). Open the source and check it against what is on this page.
experimental reaction archive record ord-1cf3f1a64d944eabb1ba184483ae76fd 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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Where to next
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