Buchwald–Hartwig amination: 4-chloro-N-[(1S)-1-(5-fluoropyrimidin-2-yl)ethyl]-6-morpholin-4-yl-1,3,5-triazin-2-amine → N-[(1S)-1-(5-Fluoropyrimidin-2-yl)ethyl]-N'-(5-methyl-1,3-thiazol-2-yl)-6-morpholin-4-yl-1,3,5-triazine-2,4-diamine
21% yield, run at 95 °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-[(1S)-1-(5-fluoropyrimidin-2-yl)ethyl]-6-morpholin-4-yl-1,3,5-triazin-2-amine | C₁₃H₁₅ClFN₇O | |
| Reactant | 2-Amino-5-methylthiazole | C₄H₆N₂S | |
| Reagent | Cesium carbonate | CCs₂O₃ | |
| Catalyst | Binap, (A+-)- | C₄₄H₃₂P₂ | |
| Catalyst | Bis(dibenzylideneacetone)palladium | C₅₁H₄₂O₃Pd₂ | |
| Solvent | 1,4-Dioxane | C₄H₈O₂ | |
| Product | N-[(1S)-1-(5-Fluoropyrimidin-2-yl)ethyl]-N'-(5-methyl-1,3-thiazol-2-yl)-6-morpholin-4-yl-1,3,5-triazine-2,4-diamine | C₁₇H₂₀FN₉OS | 20.67% |
Conditions
- Temperature
- 95 °C
Yield
- 21% of N-[(1S)-1-(5-Fluoropyrimidin-2-yl)ethyl]-N'-(5-methyl-1,3-thiazol-2-yl)-6-morpholin-4-yl-1,3,5-triazine-2,4-diamine.
Procedure
Copied from the source record, unedited
(S)-4-chloro-N-(1-(5-fluoropyrimidin-2-yl)ethyl)-6-morpholino-1,3,5-triazin-2-amine (100 mg, 0.29 mmol), 5-methylthiazol-2-amine (50.4 mg, 0.44 mmol), BINAP (18.33 mg, 0.03 mmol), Pd2(dba)3 (13.48 mg, 0.01 mmol) and Cs2CO3 (240 mg, 0.74 mmol) were combined in a microwave reaction tube and vacuum purged. The tube was then charged with nitrogen and dioxane (0.589 mL) was added. The tube was then evacuated again and placed under a nitrogen balloon for 8 hours. LC/MS confirmed formation of the product (m+1 = 418) at t= 2.07 min. The reaction mixture was concentrated in vacuo leaing a brown solid (472 mg). This material was the redissolved in EtOAc, filtered through Celite, washed with water and dried with Na2SO4. Concentration in vacuo gave a rust solid (272 mg). This material was purified by
The source
This record comes from experimental reaction archive (ord-9f0febad39ec4abd95b00a68a93da5f3). Open the source and check it against what is on this page.
experimental reaction archive record ord-9f0febad39ec4abd95b00a68a93da5f3 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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