Ethanol → 2-chloro-5-[3-(3-hydroxy-propylamino)-propoxy]-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-benzamide
反応式
[Cl:1][C:2]1[CH:21]=[CH:20][C:19]([O:22][CH2:23][CH2:24][CH2:25]Cl)=[CH:18][C:3]=1[C:4]([NH:6][CH2:7][C:8]12[CH2:17][CH:12]3[CH2:13][CH:14]([CH2:16][CH:10]([CH2:11]3)[CH2:9]1)[CH2:15]2)=[O:5].C([N:30]([CH2:34][CH3:35])C(C)C)(C)C.[I-].[Na+].[CH2:38]([OH:40])C>>[Cl:1][C:2]1[CH:21]=[CH:20][C:19]([O:22][CH2:23][CH2:24][CH2:25][NH:30][CH2:34][CH2:35][CH2:38][OH:40])=[CH:18][C:3]=1[C:4]([NH:6][CH2:7][C:8]12[CH2:9][CH:10]3[CH2:16][CH:14]([CH2:13][CH:12]([CH2:11]3)[CH2:17]1)[CH2:15]2)=[O:5]参加物
反応条件
- 温度
- 120 °C
実験手順
To a solution of 2-chloro-5-[3-chloropropoxy]-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-benzamide (0.25 g, Example 3a) and N,N-diisopropylethylamine (0.54 ml) in ethanol (5 ml) was added sodium iodide (0.08 g) and 1-propanolamine (0.24 ml). The reaction vessel was sealed and reaction mixture heated at 120° C. for 24 h. The reaction mixture was then concentrated under reduced pressure. The residue was partitioned between ethyl acetate and sodium hydrogencarbonate solution, and the aqueous phase extracted with additional ethyl acetate. The combined organic phases were dried (MgSO4) and concentrated under reduced pressure. The residue was purified by NPHPLC (eluting with 0-25% ethanol in dichloromethane) to give 2-chloro-5-[3-(3-hydroxy-propylamino)-propoxy]-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-benzamide as a semi-solid. This compound was converted to the hydrochloride salt by stirring with 4M HCl in dioxane and concentrated under reduced pressure to leave the title compound as a white solid (0.036 g).
後処理
- customThe reaction vessel was sealed
- customreaction mixture
- concentrationThe reaction mixture was then concentrated under reduced pressure
- customThe residue was partitioned between ethyl acetate and sodium hydrogencarbonate solution
- extractionthe aqueous phase extracted with additional ethyl acetate
- dry with materialThe combined organic phases were dried (MgSO4)
- concentrationconcentrated under reduced pressure
- customThe residue was purified by NPHPLC (eluting with 0-25% ethanol in dichloromethane)
出典と根拠
- ORDレコード
- ord-31e9a60501f646f8863522b100d4c0cc
- 出典データセット
- uspto-grants-2004_04
- 特許番号
- US06720452B2
反応ノート
読み込み中…