Buchwald–Hartwig amination: 4-chloro-N-phenylpyridin-2-amine → 4-N-[(2,6-difluorophenyl)methyl]-2-N-phenylpyridine-2,4-diamine
21% yield, run at 150 °C, as recorded by experimental reaction archive. The written procedure is below. One of 2 recorded runs making this product; all of them are compared below.
The atoms, from reactants to products
What was in the flask
| Role | Species | Formula | Yield |
|---|---|---|---|
| Reactant | 4-chloro-N-phenylpyridin-2-amine | C₁₁H₉ClN₂ | |
| Reactant | 2,6-Difluorobenzylamine | C₇H₇F₂N | |
| 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 | 1,2-Dimethoxyethane | C₄H₁₀O₂ | |
| Product | 4-N-[(2,6-difluorophenyl)methyl]-2-N-phenylpyridine-2,4-diamine | C₁₈H₁₅F₂N₃ | 21.04% |
Conditions
- Temperature
- 150 °C
Yield
- 21% of 4-N-[(2,6-difluorophenyl)methyl]-2-N-phenylpyridine-2,4-diamine.
Every recorded run making this product
2 runs of this class made the same product and differed in what else was in the flask. They are listed from the highest yield down, with this page's run marked.
| Catalyst | Reagents | Solvent | Temp. | Time | Yield |
|---|---|---|---|---|---|
| (R)-(-)-1-[(S)-2-(Dicyclohexylphosphino)ferrocenyl]ethyldi-t-butylphosphine;Ferrocene, 1-[(1R)-1-[bis(1,1-dimethylethyl)phosphino]ethyl]-2-(dicyclohexylphosphino)-, (2R)-; Palladium (II) acetate | sodium 2-methylpropan-2-olate | Dimethylacetamide | 100 °C | — | 61% |
| (R)-(-)-1-[(S)-2-(Dicyclohexylphosphino)ferrocenyl]ethyldi-t-butylphosphine;Ferrocene, 1-[(1R)-1-[bis(1,1-dimethylethyl)phosphino]ethyl]-2-(dicyclohexylphosphino)-, (2R)-; Palladium (II) acetate | sodium 2-methylpropan-2-olate | 1,2-Dimethoxyethane | 150 °C | — | 21% (this run) |
Procedure
Copied from the source record, unedited
4-chloro-N-phenylpyridin-2-amine (100 mg, 0.49 mmol), (2,6-difluorophenyl)methanamine (91 mg, 0.64 mmol), (R)-(-)-1-[(S)-2-(DICYCLOHEXYLPHOSPHINO)FERROCENYL]ETHYLDI-T-BUTYLPHOSPHINE (32.5 mg, 0.06 mmol),sodium 2-methylpropan-2-olate (94 mg, 0.98 mmol) and diacetoxypalladium (8.78 mg, 0.04 mmol) were suspended in DME (2.0 mL) and sealed into a microwave tube. The reaction was heated to 150 °C for 20 minutes in the microwave reactor and cooled to RT. The crude product was purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 7M NH3/MeOH and fractions were evaporated to dryness to afford crude product. The crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5µ silica, 50 mm diameter, 100 mm length), u
The source
This record comes from experimental reaction archive (ord-7d0087e63ad44356ba79974b84233090). Open the source and check it against what is on this page.
experimental reaction archive record ord-7d0087e63ad44356ba79974b84233090 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.
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