Participants
| Role | Name | HCID | Charge |
|---|
| Reactant | Bromide ion | HCID 259 | — |
| Reactant | Potassium Acetate | HCID 517044 | — |
| Reactant | Bis(pinacolato)diborane | HCID 2733548 | — |
| Reactant | N-(5-bromo-2-methoxypyridin-3-yl)-2,4-difluorobenzenesulfonamide | HCID 59859951 | — |
| Reactant | 6-Bromo-4-(pyridazin-4-yl)quinoline | HCID 66782308 | — |
| Catalyst | HCID 178418807 | HCID 178418807 | — |
| Solvent | 1,4-Dioxane | HCID 31275 | — |
| Product | Omipalisib | HCID 25167777 | 76.6% |
Reaction Steps
A slurry of 6-bromo-4-(4-pyridazinyl)quinoline (4.8 g, 16.78 mmol), bis(pinacolato)diboron (4.69 g, 18.45 mmol), PdCl2(dppf)-CH2Cl2 (530 mg, 0.649 mmol) and potassium acetate (3.29 g, 33.6 mmol) in anhydrous 1,4-dioxane (120 ml) was heated at 100° C. for 3 h. The complete disappearance of the starting bromide was observed by LCMS. The reaction was then treated with N-[5-bromo-2-(methyloxy)-3-pyridinyl]-2,4-difluorobenzenesulfonamide (6.68 g, 17.61 mmol) and another portion of PdCl2(dppf)-CH2Cl2 (550 mg, 0.673 mmol), then heated at 110° C. for 16 h. The reaction was allowed to cool to room temperature, filtered, and concentrated. Purification of the residue by chromatography (Analogix; 5% MeOH/5% CH2Cl2/90% EtOAC) gave 6.5 g (76%) desired product. MS (ES)+ m/e 505.9 [M+H]+.
Provenance & Evidence
| DOI | 10.6084/m9.figshare.5104873.v1 |
|---|
| Patent number | US08633187B2 |
|---|
| Source dataset | uspto-grants-2014_01 |
|---|
| ORD ID | ord-c2e43ffae58c4b42920c7a1bf53cd842 |
|---|
| Source note | uspto-grants-2014_01 |
|---|
