Buchwald–Hartwig amination: 7-Bromo-4-[(2-fluoro-4-methylphenyl)amino]cinnoline-3-carbonitrile → 4-(2-Fluoro-4-methylphenylamino)-7-(piperazin-1-yl)cinnoline-3-carbonitrile
51% 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 | 7-Bromo-4-[(2-fluoro-4-methylphenyl)amino]cinnoline-3-carbonitrile | C₁₆H₁₀BrFN₄ | |
| Reactant | Piperazine | C₄H₁₀N₂ | |
| Reagent | sodium 2-methylpropan-2-olate | C₄H₉NaO | |
| Catalyst | 2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl | C₃₃H₄₉P | |
| Catalyst | Bis(dibenzylideneacetone)palladium | C₅₁H₄₂O₃Pd₂ | |
| Solvent | Dimethylacetamide | C₄H₉NO | |
| Product | 4-(2-Fluoro-4-methylphenylamino)-7-(piperazin-1-yl)cinnoline-3-carbonitrile | C₂₀H₁₉FN₆ | 50.66% |
Conditions
- Temperature
- 100 °C
Yield
- 51% of 4-(2-Fluoro-4-methylphenylamino)-7-(piperazin-1-yl)cinnoline-3-carbonitrile.
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.
- tert-butyl N-[2-chloro-5-(piperazin-1-yl)phenyl]carbamate57%
- 1-(2,2-Difluoro-2H-1,3-benzodioxol-5-YL)piperazine51%
- 1-(2-Chlorophenyl)piperazine44%
- 1-(4-Methyl-3-nitrophenyl)piperazine39%
- 1-(Pyridin-3-yl)piperazine0%
- 4-Piperazin-1-yl-1-benzofuran-2-carboxamide0%
- 4-Chloro-2-(piperazin-1-yl)benzonitrile0%
- 4-Fluoro-2-(piperazin-1-yl)benzonitrile0%
Procedure
Copied from the source record, unedited
A 1L flask was charged with 7-bromo-4-(2-fluoro-4-methylphenylamino)cinnoline-3-carbonitrile (3.93 g, 11.00 mmol), Piperazine (3.88 ml, 49.51 mmol), Tris(dibenzylideneacetone)dipalladium (0) (0.806 g, 0.88 mmol), 2-Dicyclohexylphosphino-2',4',6'-tri-iso-propyl-1,1'-biphenyl (0.787 g, 1.65 mmol) and Sodium tert-butoxide (3.37 ml, 27.51 mmol). The atmosphere was evacuated and replaced with N2(g) and DMA (157 ml) was added to the mixture. The reaction mixture was stirred at 100 °C for 1h. The reaction mixture was cooled to rt, adsorbed on silica gel and flash chromatography using DCM to DCM/MeOH/NH4OH (10:1:0.1) provided the desired adduct as a light brown solid.
The source
This record comes from experimental reaction archive (ord-b790a1db0b324eea8d1b75eaa501512c). Open the source and check it against what is on this page.
experimental reaction archive record ord-b790a1db0b324eea8d1b75eaa501512c 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
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