Water → HCID 46198728、化合物

HRID 1091330ノート

反応式

HRID 1091330 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.C1N=CN([C:31](N2C=NC=C2)=[O:32])C=1.[NH:38]1[C:42]2[CH:43]=[CH:44][CH:45]=[CH:46][C:41]=2[N:40]=[C:39]1[C:47]1[CH:48]=[C:49]([NH2:54])[CH:50]=[CH:51][C:52]=1[Cl:53].O>CN(C=O)C.CCOCC>[NH:38]1[C:42]2[CH:43]=[CH:44][CH:45]=[CH:46][C:41]=2[N:40]=[C:39]1[C:47]1[CH:48]=[C:49]([NH:54][C:31]([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:32])[CH:50]=[CH:51][C:52]=1[Cl:53]

参加物

7

反応物 4

HCID 962WaterHCID 682631,1'-CarbonyldiimidazoleHCID 2788313-(1H-benzimidazol-2-yl)-4-chloroanilineHCID 866307653-(5-(Aminomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione methanesulfonate

生成物 1

HCID 46198728HCID 46198728、化合物収率 22%

試薬・触媒・溶媒 2

HCID 3283Diethyl Ether溶媒HCID 6228Dimethylformamide溶媒

実験手順

A mixture of 3-(5-aminomethyl-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione methanesulfonic acid salt (0.40 g, 1.1 mmol) and CDI (0.21 g, 1.3 mmol) in DMF (5 mL) was stirred at room temperature for 18 h. To the mixture was added 3-(1H-benzoimidazol-2-yl)-4-chloro-phenylamine (0.32 g, 1.3 mmol) at room temperature, and the mixture was stirred at 100° C. for 18 hours. To the mixture was added water (25 mL) and ether (20 mL). The mixture was stirred at room temperature for 2 h. The solvent was decanted. The solid was purified with Prep HPLC to give 1-[3-(1H-benzoimidazol-2-yl)-4-chloro-phenyl]-3-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-urea as a white solid (130 mg, 22% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 20/80 CH3CN/0.1% H3PO4, 4.44 min (99.2%); mp: 275-277° C.; 1H NMR (DMSO-d6) δ 1.90-2.10 (m, 1H, CHH), 2.23-2.46 (m, 1H, CHH), 2.54-2.68 (m, 1H, CHH), 2.80-3.02 (m, 1H, CHH), 4.31 (d, J=17.4 Hz, 1H, CHH), 4.37-4.51 (m, 3H, CHH, CH2), 5.11 (dd, J=5.0, 13.3 Hz, 1H, NCH), 6.89 (t, J=5.9 Hz, 1H, NH), 7.23 (d, J=4.5 Hz, 2H, Ar), 7.40-7.76 (m, 7H, Ar), 8.07 (d, J=2.5 Hz, 1H, Ar), 9.02 (s, 1H, NH), 10.98 (s, 1H, NH), 12.64 (br. s., 1H, NH); 13C NMR (DMSO-d6) δ 22.39, 31.10, 42.75, 47.02, 51.48, 111.62, 118.88, 120.11, 120.62, 121.55, 121.83, 122.56, 122.85, 126.85, 129.79, 130.23, 130.35, 134.56, 139.56, 142.29, 143.00, 144.58, 149.12, 154.96, 162.96, 167.86, 170.91, 172.76; LCMS MH=543, 545; Anal. Calcd for C28H21N6O4Cl+3H2O: C, 56.33; H, 4.90; N, 14.08. Found: C, 56.73; H, 4.67; N, 14.09.

後処理

  1. stirringthe mixture was stirred at 100° C. for 18 hours
  2. stirringThe mixture was stirred at room temperature for 2 h
  3. customThe solvent was decanted
  4. customThe solid was purified with Prep HPLC

出典と根拠

ORDレコード
ord-b2621fcb9ed140cbbbbb6144bf6fb7eb
出典データセット
uspto-grants-2012_03
特許番号
US08129375B2

反応ノート

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