1,8-Diazabicyclo(5.4.0)undec-7-ene → HCID 58827305, 화합물

HRID 448482노트

반응식

HRID 448482 반응식
Cl.[NH2:2][CH2:3][C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[C:6](=[O:22])[N:7]([CH:14]1[CH2:19][CH2:18][C:17](=[O:20])[NH:16][C:15]1=[O:21])[C:8]2=[O:13].N12CCCN=C1CCCCC2.[F:34][C:35]1[CH:36]=[C:37]([CH2:42][C:43](O)=[O:44])[CH:38]=[CH:39][C:40]=1[CH3:41].Cl.CN(C)CCCN=C=NCC>C(#N)C>[O:21]=[C:15]1[CH:14]([N:7]2[C:6](=[O:22])[C:5]3[C:9](=[CH:10][CH:11]=[CH:12][C:4]=3[CH2:3][NH:2][C:43](=[O:44])[CH2:42][C:37]3[CH:38]=[CH:39][C:40]([CH3:41])=[C:35]([F:34])[CH:36]=3)[C:8]2=[O:13])[CH2:19][CH2:18][C:17](=[O:20])[NH:16]1

참가 물질

6

반응물 4

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27746183-Fluoro-4-methylphenylacetic acidHCID 219885254-(aminomethyl)-2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione hydrochloride

생성물 1

HCID 58827305HCID 58827305, 화합물수율 72.7%

시약·촉매·용매 1

HCID 6342Acetonitrile용매

실험 절차

To a stirred suspension of 4-aminomethyl-2-(2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dione hydrochloride (0.7 g, 2.2 mmol) in acetonitrile (60 mL), was added 1,8-diazabicyclo[5,4,0]undec-7-ene (0.8 g, 5.4 mmol). After stirring for 10 minutes, 1-hydroxybenzotraiazole (0.4 g, 2.6 mmol) and 3-fluoro-4-methylphenylacetic acid (0.4 g, 2.4 mmol) were added, followed by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.6 g, 3.2 mmol). The mixture was stirred at room temperature overnight then was concentrated in vacuo. The residue was dissolved in CH2Cl2 (80 mL) and washed with water (40 mL), 1NHCl (2×30 mL), water (40 mL), and brine (40 mL), and dried over MgSO4. Solvent was removed in vacuo, and the residue was purified by ISCO silica gel flash chromatography (Eluent: EtOAc: CH2Cl2 3:7) to afford N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-2-(3-fluoro-4-methyl-phenyl)-acetamide (0.7 g, 70%) as a white solid: mp 148-150° C.; HPLC: Waters Symmetry C-18, 3.9×150 mm, 5 micro, 1 mL/min, 240 nm, 40/60 (CH3CN/H2O): tR=4.06 min. (98%); 1H NMR (DMSO-d6) δ 2.04-2.07 (m, 1H), 2.20 (s, 3H), 2.52-2.63 (m, 2H), 2.84-2.96 (m, 1H), 3.52 (s, 2H), 4.70 (d, J=5.7 Hz, 2H), 5.12-5.18 (dd, J=5.1 and 12.7 Hz, 1H), 6.99-7.07 (dd, J=11.2 and 14.7 hz, 2H), 7.21 (t, J=8.0 Hz, 1H), 7.63-7.76 (dd, J=3.3 and 7.5 Hz, 1H), 7.77-7.83 (dd, J=7.6 and 11.9 Hz, 2H), 8.65 (t, J=5.8 Hz, 1H), 11.14 (s, 1H); 13C NMR (DMSO-d6) δ 13.74 (13.78), 21.95, 30.90, 37.84, 41.41, 48.83, 115.31, 115.60, 121.89, 124.84 (124.87), 127.12, 131.02 (131.28), 131.51, 133.20, 134.66, 135.87 (135.97), 139.09, 158.77 (161.98), 166.90, 167.42, 169.78, 170.26, 172.73; Anal. Calcd. for C23H20N3O5F: C, 63.15; H, 4.61; N, 9.61; F, 4.34. Found: C, 62.78; H, 4.45; N, 9.32; F, 4.47.

후처리

  1. stirringThe mixture was stirred at room temperature overnight
  2. concentrationthen was concentrated in vacuo
  3. dissolutionThe residue was dissolved in CH2Cl2 (80 mL)
  4. washwashed with water (40 mL), 1NHCl (2×30 mL), water (40 mL), and brine (40 mL)
  5. dry with materialdried over MgSO4
  6. customSolvent was removed in vacuo
  7. customthe residue was purified by ISCO silica gel flash chromatography (Eluent: EtOAc: CH2Cl2 3:7)

출처 및 근거

ORD 기록
ord-9e6261bca2e6473b8cb8e8807356822d
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08481568B2

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