Hydrochloric Acid → 1-(3,5-Dichloro-phenyl)-3-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1h-isoindol-5-ylmethyl]-urea

HRID 331644

반응식

HRID 331644 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.[Cl:26][C:27]1[CH:28]=[C:29]([N:34]=[C:35]=[O:36])[CH:30]=[C:31]([Cl:33])[CH:32]=1.C(N(CC)CC)C.Cl>C(#N)C>[Cl:26][C:27]1[CH:28]=[C:29]([NH:34][C:35]([NH:6][CH2:7][C:8]2[CH:9]=[C:10]3[C:14](=[CH:15][CH:16]=2)[C:13](=[O:17])[N:12]([CH:18]2[CH2:23][CH2:22][C:21](=[O:24])[NH:20][C:19]2=[O:25])[CH2:11]3)=[O:36])[CH:30]=[C:31]([Cl:33])[CH:32]=1

참가 물질

6

반응물 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 944603,5-Dichlorophenyl isocyanateHCID 866307653-(5-(Aminomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione methanesulfonate

생성물 1

HCID 577305101-(3,5-Dichloro-phenyl)-3-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1h-isoindol-5-ylmethyl]-urea수율 78%

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 (0.37 g, 1.0 mmol) and 3,5-dichlorophenylisocyanate (0.19 g, 1.0 mmol) in acetonitrile (10 mL), was added triethylamine (0.28 mL, 2.0 mmol) at room temperature under nitrogen. After 18 h, 1 N aq. HCl (10 mL) was added and the solids were isolated by filtration and washed with water (40 mL). The solids were triturated in EtOAc (10 mL) for 18 h, then isolated by filtration, washed with EtOAc (40 mL) and dried in vacuo to give 1-(3,5-dichloro-phenyl)-3-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-urea as a white solid (0.36 g, 78% 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, 9.14 min (96.29%); mp: 274-276° C.; 1H NMR (DMSO-d6) δ 1.86-2.12 (m, 1H, CHH), 2.24-2.47 (m, 1H, CHH), 2.60 (d, J=16.4 Hz, 1H, CHH), 2.77-3.05 (m, 1H, CHH), 4.31 (d, J=17.4 Hz, 1H, CHH), 4.38-4.56 (m, 3H, CHH, CH2), 5.11 (dd, J=5.1, 13.2 Hz, 1H, CH), 7.00 (t, J=5.9 Hz, 1H, NH), 7.08 (t, J=1.7 Hz, 1H, Ar), 7.44 (d, J=7.7 Hz, 1H, Ar), 7.48-7.59 (m, 3H, Ar), 7.70 (d, J=7.7 Hz, 1H, Ar), 9.08 (s, 1H, NH), 10.99 (s, 1H, NH); 13C NMR (DMSO-d6) δ 22.49, 31.20, 42.83, 47.12, 51.58, 115.78, 120.16, 121.92, 122.94, 126.92, 130.35, 133.93, 142.39, 142.93, 144.43, 154.77, 167.92, 170.98, 172.85; LCMS: MH=461/463/465; Anal Calcd for C21H18N4O4Cl2: C, 54.68; H, 3.93; N, 12.15; Cl, 15.37. Found: C, 54.61; H, 3.78; N, 11.84; Cl, 15.10.

후처리

  1. customthe solids were isolated by filtration
  2. washwashed with water (40 mL)
  3. customThe solids were triturated in EtOAc (10 mL) for 18 h
  4. customisolated by filtration
  5. washwashed with EtOAc (40 mL)
  6. customdried in vacuo

출처 및 근거

ORD 기록
ord-4c6de45b6e8c43b2909f02bcf12b9621
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08877780B2

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