関与物質
| 役割 | 名称 | HCID | 仕込み量 |
|---|
| 反応物 | Benzyl Alcohol | HCID 244 | — |
| 反応物 | Hydrochloric Acid | HCID 313 | — |
| 反応物 | Dimethylformamide | HCID 6228 | — |
| 反応物 | 1,4-Dioxane | HCID 31275 | — |
| 反応物 | Diisopropylethylamine | HCID 81531 | — |
| 反応物 | Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) | HCID 9886157 | — |
| 反応物 | (2R,4R)-4-amino-5-(3'-chlorobiphenyl-4-yl)-2-hydroxypentanoic acid ethyl ester | HCID 86682253 | — |
| 反応物 | HCID 178481916 | HCID 178481916 | — |
| 生成物 | HCID 178481915 | HCID 178481915 | 70.6% |
反応手順
A mixture of (2R,4R)-4-amino-5-(3′-chlorobiphenyl-4-yl)-2-hydroxypentanoic acid ethyl ester (150.0 mg, 431 μmol), benzyl alcohol (446.2 μL, 4.3 mmol), and 4.0 M HCl in 1,4-dioxane (431 μL, 1.7 mmol) was stirred at room temperature overnight, then at 50° C. for 1 hour. The mixture was then concentrated under reduced pressure. 5-Hydroxy-1-methyl-1H-pyrazole-3-carboxylic acid (30.6 mg, 216 μmol) and HATU (98.4 mg, 259 mol) were stirred in DMF (0.5 mL, 5 mmol) for 10 minutes, then added to the concentrated mixture, along with DIPEA (113 μL, 647 μmol). The resulting mixture was stirred at room temperature for 2 hours and concentrated under reduced pressure. The residue was dissolved in 50% AcOH-water (5 mL), filtered, and purified by reverse phase preparative HPLC to yield the title compound (81.4 mg).
情報源と証拠
| DOI | 10.6084/m9.figshare.5104873.v1 |
|---|
| 特許番号 | US09108934B2 |
|---|
| 出典データセット | uspto-grants-2015_08 |
|---|
| ORD ID | ord-945fb1eee10847f7959ea2fa4148f6c5 |
|---|
| 出典メモ | uspto-grants-2015_08 |
|---|
