Buchwald–Hartwig amination: 4-Bromo-1-(4-fluorophenyl)-1H-indazole → N-[(2S)-1-[[1-(4-fluorophenyl)indazol-4-yl]amino]-3-methylbutan-2-yl]-2,4,6-trimethylbenzenesulfonamide
11% yield, run at 110 °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-Bromo-1-(4-fluorophenyl)-1H-indazole | C₁₃H₈BrFN₂ | |
| Reactant | Cc1cc(C)c(S(=O)(=O)N[C@H](CN)C(C)C)c(C)c1 | C₁₄H₂₄N₂O₂S | |
| Reagent | sodium 2-methylpropan-2-olate | C₄H₉NaO | |
| Catalyst | Binap, (A+-)- | C₄₄H₃₂P₂ | |
| Catalyst | Bis(dibenzylideneacetone)palladium | C₅₁H₄₂O₃Pd₂ | |
| Solvent | Toluene | C₇H₈ | |
| Product | N-[(2S)-1-[[1-(4-fluorophenyl)indazol-4-yl]amino]-3-methylbutan-2-yl]-2,4,6-trimethylbenzenesulfonamide | C₂₇H₃₁FN₄O₂S | 11.38% |
Conditions
- Temperature
- 110 °C
Yield
- 11% of N-[(2S)-1-[[1-(4-fluorophenyl)indazol-4-yl]amino]-3-methylbutan-2-yl]-2,4,6-trimethylbenzenesulfonamide.
Procedure
Copied from the source record, unedited
BINAP (0.432 g, 0.69 mmol) and Pd2(dba)3 (0.24 g, 0.26 mmol) were dissolved in toluene (10 mL) and to this (S)-N-(1-amino-3-methylbutan-2-yl)-2,4,6-trimethylbenzenesulfonamide (0.856 g, 3.01 mmol) and 4-bromo-1-(4-fluorophenyl)-1H-indazole (0.876 g, 3.01 mmol) was added followed by sodium tert-butoxide (0.434 g, 4.51 mmol). The reaction mixture was degassed and the reaction tube was filled with nitrogen before it was heated at 110°C for 2h. LCMS indicated 55% product and just a small amout of starting materials remained. The reaction was partitioned between EtOAc and water. The layers were separated and the aqueous extracted twice with EtOAc. The organic extracts were combined, filtered through a fine sinter funnel to remove a grey ppte and then dried using a phase separator cartridge. The
The source
This record comes from experimental reaction archive (ord-91d62f2c93df477a8b3df11f707f23e4). Open the source and check it against what is on this page.
experimental reaction archive record ord-91d62f2c93df477a8b3df11f707f23e4 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
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