関与物質
| 役割 | 名称 | HCID | 仕込み量 |
|---|
| 反応物 | Hydrochloric Acid | HCID 313 | — |
| 反応物 | Diisopropylethylamine | HCID 81531 | — |
| 反応物 | 4-Carboxy-1,2,3-triazole | HCID 140120 | — |
| 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 | (2S,4R)-5-Biphenyl-4-yl-4-t-butoxycarbonylamino-2-hydroxymethyl-2-methyl-pentanoic acid | HCID 68181022 | — |
| 溶媒 | Ethanol | HCID 702 | — |
| 溶媒 | Dimethylformamide | HCID 6228 | — |
| 溶媒 | 1,4-Dioxane | HCID 31275 | — |
| 生成物 | HCID 178471713 | HCID 178471713 | — |
反応手順
1,2,3-Triazole-4-carboxylic acid (11.5 mg, 102 nmol, 1.2 eq.) and HATU (38.6 mg, 102 nmol, 1.2 eq.) were dissolved in DMF (0.9 mL) and stirred at room temperature for 5 minutes. DIPEA (29.5 μL, 2.0 eq.) was added to yield the activated acid. (2S,4R)-5-Biphenyl-4-yl-4-t-butoxycarbonylamino-2-hydroxymethyl-2-methyl-pentanoic acid (35 mg, 85 μmol, 1.0 eq.) was dissolved in EtOH and 4 M of HCl in dioxane (423 μL) was added. The mixture was heated to 60° C. overnight, then concentrated to dryness and purified by reverse phase chromatography (5-60% MeCN in water over 18 minutes. The clean fractions were combined and dried under vacuum to dryness, then combined with the activated acid. After 20 minutes, the reaction was quenched with water and the product was dried under vacuum and purified by preparative HPLC to yield the title compound (4 mg, >95% purity. MS m/z [M+H]+ calc'd for C24H28N4O4, 437.21. found 437.3.
情報源と証拠
| DOI | 10.6084/m9.figshare.5104873.v1 |
|---|
| 特許番号 | US08481044B2 |
|---|
| 出典データセット | uspto-grants-2013_07 |
|---|
| ORD ID | ord-3eec78ea48ab4fcfba69b65b1267a2de |
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| 出典メモ | uspto-grants-2013_07 |
|---|
