Hydrochloric Acid → N-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-4-ethoxy-benzamide

HRID 331578ノート

反応式

HRID 331578 の反応式
CS(O)(=O)=O.[NH2:6][CH2:7][C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[C:13](=[O:17])[N:12]([CH:18]1[CH2:23][CH2:22][C:21](=[O:24])[NH:20][C:19]1=[O:25])[CH2:11]2.[CH2:26]([O:28][C:29]1[CH:37]=[CH:36][C:32]([C:33](Cl)=[O:34])=[CH:31][CH:30]=1)[CH3:27].Cl>C(#N)C>[O:25]=[C:19]1[CH:18]([N:12]2[CH2:11][C:10]3[C:14](=[CH:15][CH:16]=[C:8]([CH2:7][NH:6][C:33](=[O:34])[C:32]4[CH:31]=[CH:30][C:29]([O:28][CH2:26][CH3:27])=[CH:37][CH:36]=4)[CH:9]=3)[C:13]2=[O:17])[CH2:23][CH2:22][C:21](=[O:24])[NH:20]1

参加物

5

反応物 3

HCID 313Hydrochloric AcidHCID 1400594-Ethoxybenzoyl ChlorideHCID 866307653-(5-(Aminomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione methanesulfonate

生成物 1

HCID 44538213N-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-4-ethoxy-benzamide収率 46%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

実験手順

To a stirred mixture of 3-(5-aminomethyl-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione methanesulfonate (0.50 g, 1.4 mmol) and 4-ethoxybenzoyl chloride (0.26 g, 1.4 mmol) in acetonitrile (30 mL) at 0° C. was added TEA (0.28 g, 2.8 mmol) dropwise over 10 min. The mixture was stirred at ambient temperature for 2 h and then 10% aqueous HCl solution (30 mL) was added. The solid precipitate was filtered and purified by column chromatography (C18 reverse phase column). The product fractions were combined, concentrated and dried in vacuo providing N-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-4-ethoxy-benzamide as a white solid (0.26 g, 46% yield); mp 269-271° C.; HPLC, Waters Symmetry C-18, 3.9×150 mm, 5 μm, 1 ml/min, 240 nm, 30/70 CH3CN/0.1% H3PO4, 5.75 (96.56%); 1H NMR (DMSO-d6) δ 1.34 (t, 3H, CH3), 1.90-2.08 (m, 1H, CHH), 2.27-2.45 (m, 1H, CHH), 2.55-2.68 (m, 1H, CHH), 2.80-3.03 (m, 1H, CHH), 4.09 (q, 2H, CH2), 4.30 (d, 1H, CHH), 4.41 (d, 1H, CHH), 4.58 (d, 2H, CH2 and CHH), 5.10 (dd, J=4.5, 13.0 Hz, 1H, CH), 6.99 (d, J=8.3 Hz, 2H, Ar), 7.44 (d, 1H, Ar), 7.54 (s, 1H, Ar), 7.69 (d, 1H, Ar), 7.87 (d, J=8.5 Hz, 2H, Ar), 8.99 (t, 1H, NH), 10.98 (s, 1H, NH); 13C NMR (DMSO-d6) δ 14.53, 22.49, 31.18, 42.64, 47.12, 51.56, 63.28, 113.92, 122.01, 122.90, 126.19, 127.02, 129.09, 130.30, 142.35, 144.20, 160.92, 165.75, 167.93, 170.98, 172.85; LCMS: MH=422; Anal. Calcd for C23H23N3O5+0.5H2O: C, 64.18; H, 5.62; N, 9.76. Found: C, 64.03; H, 5.45; N, 9.63.

後処理

  1. filtrationThe solid precipitate was filtered
  2. custompurified by column chromatography (C18 reverse phase column)
  3. concentrationconcentrated
  4. customdried in vacuo

出典と根拠

ORDレコード
ord-49196119346142dbab51e77bf600dfc3
出典データセット
uspto-grants-2014_11
特許番号
US08877780B2

反応ノート

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