Buchwald–Hartwig amination, record ord-135c33d2da2b4d7f90276e4b49e654c9
One recorded run of this reaction. Below is what the source recorded, and nothing added to it.
What was in the flask
| Role | Species | Formula | Yield |
|---|---|---|---|
| Reactant | Cc1cc(Cl)ncc1-c1ccc(-c2nc3c(CO)cccc3c(=O)[nH]2)cc1 | C₂₁H₁₆ClN₃O₂ | |
| Reactant | (S)-1,2-Dimethylpiperazine | C₆H₁₄N₂ | |
| Reagent | sodium 2-methylpropan-2-olate | C₄H₉NaO | |
| Catalyst | 2-Dicyclohexylphosphino-2',6'-diisopropoxybiphenyl | C₃₀H₄₃O₂P | |
| Catalyst | (RuPhos) palladium(II) phenethylamine chloride (1:1 MTBE solvate) | C₄₃H₆₅ClNO₃PPd | |
| Solvent | 1,4-Dioxane | C₄H₈O₂ | |
| Product | 2-[4-[6-[(3S)-3,4-dimethylpiperazin-1-yl]-4-methyl-3-pyridinyl]phenyl]-8-(hydroxymethyl)-1H-quinazolin-4-one | C₂₇H₂₉N₅O₂ | 34.73% |
Conditions
- Temperature
- 115 °C
Yield
- 35% of 2-[4-[6-[(3S)-3,4-dimethylpiperazin-1-yl]-4-methyl-3-pyridinyl]phenyl]-8-(hydroxymethyl)-1H-quinazolin-4-one.
Procedure
Copied from the source record, unedited
A mixture of CHLORO(2-DICYCLOHEXYLPHOSPHINO-2',6'-DI-I- PROPOXY-1,1'-BIPHENYL)[2-(2-AMINOETHYLPHENYL)]PALLADIUM(II), METHYL-T- BUTYLETHER ADDUCT (Ru Phos Pd cycle) (69.2 mgs, 0.2eq), sodium tert-butoxide (244 mg, 2.54 mmol) ,2-(4-(6-chloro-4-methylpyridin-3-yl)phenyl)-8-(hydroxymethyl)quinazolin-4(3H)-one (200 mg, 0.42 mmol) , (S)-1,2-dimethylpiperazine (198 mg, 1.06 mmol) in dioxane (20ml) was stirred at 115°C for 1hr, LCMS indicated the completion of reaction. The solid was filtered off through a pad of celite, washed with DCM. The solvent of the filtrate was removed by concentration, taken into 2ml of DMSO, purified with reverse phase chromatography column (eluted with 5% to 50% 0.1%TFA in ACN/0.1%TFA in water), the fractions were combined and lyphlized, to yield 117mgs of product. LCMS
The source
This record comes from experimental reaction archive (ord-135c33d2da2b4d7f90276e4b49e654c9). Open the source and check it against what is on this page.
experimental reaction archive record ord-135c33d2da2b4d7f90276e4b49e654c9 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.