Water → HCID 46198728, 화합물

HRID 588030노트

반응식

HRID 588030 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.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]

참가 물질

7

반응물 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

생성물 1

HCID 46198728HCID 46198728, 화합물수율 22%

시약·촉매·용매 2

HCID 3283Diethyl Ether용매HCID 6228Dimethylformamide용매

실험 절차

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 C28H23N6O4Cl+3H2O: C, 56.33: H, 4.90; N, 14.08. Found: C, 56.73; H, 4.67; N, 14.09.

후처리

  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

출처 및 근거

ORD 기록
ord-f785c970b13445d78c788ec8205ba436
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09227954B2

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