Acetic Anhydride → N-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-acetamide

HRID 63431

반응식

HRID 63431 반응식
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.[C:26](OC(=O)C)(=[O:28])[CH3:27].C(N(CC)CC)C>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:26](=[O:28])[CH3:27])[CH:9]=3)[C:13]2=[O:17])[CH2:23][CH2:22][C:21](=[O:24])[NH:20]1

참가 물질

5

반응물 3

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 866307653-(5-(Aminomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione methanesulfonate

생성물 1

HCID 44538209N-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-acetamide수율 75%

시약·촉매·용매 1

HCID 6342Acetonitrile용매

실험 절차

To a stirred mixture of 3-(5-aminomethyl-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione methane sulfonate (0.75 g, 2.0 mmol) and acetic anhydride (0.19 mL, 2.0 mmol) in acetonitrile (20 mL), was added triethylamine (0.56 mL, 4.0 mmol) at room temperature under nitrogen. After 1 h, the solids were isolated by filtration. The crude product was triturated in water (20 mL) for 1.0 h, then isolated by filtration and dried in vacuo to give N-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-acetamide as a white solid (0.47 g, 75% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 10/90 to 90/10 CH3CN/0.1% H3PO4 gradient over 15 mins, 3.28 min (96.26%); mp: 183-185° C.; 1H NMR (DMSO-d6) δ 1.89 (s, 3H, CH3), 1.93-2.07 (m, 1H, CHH), 2.26-2.48 (m, 1H, CHH), 2.54-2.70 (m, 1H, CHH), 2.77-3.04 (m, 1H, CHH), 4.22-4.51 (m, 4H, CH2, CH2), 5.11 (dd, J=5.1, 13.2 Hz, 1H, CH), 7.39 (d, J=7.9 Hz, 1H, Ar), 7.47 (s, 1H, Ar), 7.68 (d, J=7.9 Hz, 1H, Ar), 8.45 (t, J=5.8 Hz, 1H, NH), 10.98 (s, 1H, NH); 13C NMR (DMSO-d6) δ 22.49, 22.56, 31.21, 42.14, 47.10, 51.59, 122.08, 122.90, 127.05, 130.32, 142.36, 143.95, 167.93, 169.25, 171.00, 172.86; LCMS: MH=316; Anal Calcd for C16H17N3O4: C, 60.94; H, 5.43; N, 13.33. Found: C, 60.61; H, 5.31; N, 13.30.

후처리

  1. customthe solids were isolated by filtration
  2. customThe crude product was triturated in water (20 mL) for 1.0 h
  3. customisolated by filtration
  4. customdried in vacuo

출처 및 근거

ORD 기록
ord-c16728ed464842429b9184610b4070ba
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09447070B2

연결된 노트

불러오는 중…