Buchwald–Hartwig amination: 4-chloro-N-(4-fluorophenyl)pyridin-2-amine → 4-N-benzyl-2-N-(4-fluorophenyl)pyridine-2,4-diamine
74% 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 | 4-chloro-N-(4-fluorophenyl)pyridin-2-amine | C₁₁H₈ClFN₂ | |
| Reactant | Benzylamine | C₇H₉N | |
| Reagent | sodium 2-methylpropan-2-olate | C₄H₉NaO | |
| Catalyst | (R)-(-)-1-[(S)-2-(Dicyclohexylphosphino)ferrocenyl]ethyldi-t-butylphosphine;Ferrocene, 1-[(1R)-1-[bis(1,1-dimethylethyl)phosphino]ethyl]-2-(dicyclohexylphosphino)-, (2R)- | C₃₂H₆₂FeP₂ | |
| Catalyst | Palladium (II) acetate | C₄H₈O₄Pd | |
| Solvent | Dimethylacetamide | C₄H₉NO | |
| Product | 4-N-benzyl-2-N-(4-fluorophenyl)pyridine-2,4-diamine | C₁₈H₁₆FN₃ | 74.38% |
Conditions
- Temperature
- 100 °C
Yield
- 74% of 4-N-benzyl-2-N-(4-fluorophenyl)pyridine-2,4-diamine.
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.
- 4-N-benzyl-2-N-(4-methoxyphenyl)pyridine-2,4-diamine59%
- 4-N-benzyl-2-N-phenylpyridine-2,4-diamine57%
- 6-benzylamino-3,4-dihydro-2H-isoquinolin-1-one0%
- N-Benzyl-4-chloropyridin-2-amine0%
- N-benzyl-4-methylthiazol-2-amine0%
- 4-N-benzyl-2-N-phenylpyridine-2,4-diamine13%
- 4-N-benzyl-2-N-phenylpyridine-2,4-diamine6%
- 6-benzylamino-3,4-dihydro-2H-isoquinolin-1-one0%
- 6-benzylamino-3,4-dihydro-2H-isoquinolin-1-one0%
- N-Benzyl-4-chloropyridin-2-amine0%
Procedure
Copied from the source record, unedited
Phenylmethanamine (52.9 mg, 0.49 mmol), 4-chloro-N-(4-fluorophenyl)pyridin-2-amine (100 mg, 0.45 mmol) and sodium 2-methylpropan-2-olate (86 mg, 0.90 mmol) were suspended in DMA (2 mL) and sealed into a microwave tube. Nitrogen was bubbled through the reaction mixture for 5 minutes. (R)-(-)-1-[(S)-2-(DICYCLOHEXYLPHOSPHINO)FERROCENYL]ETHYLDI-T-BUTYLPHOSPHINE (29.9 mg, 0.05 mmol) and diacetoxypalladium (8.07 mg, 0.04 mmol) were added to the reaction mixture and nitrogen was bubbled through the reaction mixture for a further 5 minutes. The reaction was heated thermally to 100 °C for 30 mins under nitrogen and cooled to RT. The reaction mixture was neutralised with HCl and purified by ion exchange chromatography, using a 20 g SCX column. The crude product was purified by flash silica chromatog
The source
This record comes from experimental reaction archive (ord-2c0a8dbc66b74712a354b7c2ed2d9d4c). Open the source and check it against what is on this page.
experimental reaction archive record ord-2c0a8dbc66b74712a354b7c2ed2d9d4c 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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