Participants
| Role | Name | HCID | Charge |
|---|
| Reactant | Cesium carbonate | HCID 10796 | — |
| Reactant | 6-Bromopyridine-3-carbonitrile | HCID 5005718 | — |
| Reactant | (S)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-3-((S)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl)-1,3-oxazinan-2-one | HCID 59532385 | — |
| Catalyst | HCID 178418476 | HCID 178418476 | — |
| Solvent | 1,4-Dioxane | HCID 31275 | — |
| Product | HCID 58109371 | HCID 58109371 | 62.7% |
Reaction Steps
To a solution of (S)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-3-((S)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl)-1,3-oxazinan-2-one (200 mg, 0.42 mmol) in 1,4-dioxane (1.5 mL) was added 6-bromonicotinonitrile (123 mg, 0.67 mmol), Pd(PPh3)2Cl2 (30 mg, 0.042 mmol), and Cs2CO3 (1 mL, 2 M) were added. The vessel was sealed with a septum and placed into the microwave cavity. Microwave irradiation of 100 W was used, and the temperature being ramped from rt to 120° C. Once this temperature was reached, the reaction mixture was held at this temperature for 30 min. After the mixture was cooled to rt, the mixture was filtered. The filtrate was extracted with EtOAc (4×20 mL). The organic layer was washed with brine, dried over Na2SO4 and concentrated to give the crude product, which was purified by preparative TLC to give 6-(4-((S)-1-((S)-6-(2-hydroxy-2-methylpropyl)-2-oxo-6-phenyl-1,3-oxazinan-3-yl)ethyl)phenyl)nicotinonitrile (120 mg, 62%). LC-MS Method 2 tR=1.33, m/z=398; 1H NMR (CDCl3): 1.13 (s, 3H), 1.19 (s, 3H), 1.58 (d, 3H), 2.22 (m, 2H), 2.27 (m, 2H), 2.40 (m, 1H), 2.89 (m, 1H), 3.49 (s, 1H), 5.73 (m, 1H), 7.11 (d, 2H), 7.28-7.38 (m, 5H), 7.80 (m, 3H), 8.00 (d, 1H), 8.93 (s, 1H).
Provenance & Evidence
| DOI | 10.6084/m9.figshare.5104873.v1 |
|---|
| Patent number | US08569292B2 |
|---|
| Source dataset | uspto-grants-2013_10 |
|---|
| ORD ID | ord-1d857714754c41c8800f36f1f53626e4 |
|---|
| Source note | uspto-grants-2013_10 |
|---|