1-Hydroxybenzotriazole → HCID 58827284, compound

HRID 448483Notes

Reaction equation

HRID 448483 reaction equation
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.ON1C2C=CC=CC=2N=N1.[CH3:44][O:45][C:46]1[CH:47]=[C:48]([CH2:54][C:55](O)=[O:56])[CH:49]=[C:50]([O:52][CH3:53])[CH:51]=1.Cl.CN(C)CCCN=C=NCC>C(#N)C>[CH3:53][O:52][C:50]1[CH:49]=[C:48]([CH2:54][C:55]([NH:2][CH2:3][C:4]2[CH:12]=[CH:11][CH:10]=[C:9]3[C:5]=2[C:6](=[O:22])[N:7]([CH:14]2[CH2:19][CH2:18][C:17](=[O:20])[NH:16][C:15]2=[O:21])[C:8]3=[O:13])=[O:56])[CH:47]=[C:46]([O:45][CH3:44])[CH:51]=1

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 138316(3,5-Dimethoxyphenyl)acetic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 219885254-(aminomethyl)-2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione hydrochloride

Product 1

HCID 58827284HCID 58827284, compoundYield 79%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

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-hydroxybenzotriazole (0.4 g, 2.6 mmol) and 3,5-dimethoxyphenylacetic acid (0.5 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 and was then 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 2-(3,5-dimethoxy-phenyl)-N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-acetamide (0.8 g, 79%) as a white solid: mp 294-296° C.; HPLC: Waters Symmetry C-18, 3.9×150 mm, 5 micro, 1 mL/min, 240 nm, 40/60 (CH3CN/H2O): tR=2.88 min. (98%); 1H NMR (DMSO-d6) δ 2.03-2.07 (m, 1H), 2.52-2.63 (m, 2H), 2.84-2.94 (m, 1H), 3.45 (s, 2H), 3.71 (s, 6H), 4.70 (d, J=5.9 Hz, 2H), 5.12-5.18 (dd, J=5.3 and 12.8 Hz, 1H), 6.37 (t, J=2.2 Hz, 1H), 6.46 (d, J=2.2 Hz, 2H), 7.51-7.67 (m, 1H), 7.72-7.81 (m, 2H), 8.61 (t, J=5.9 Hz, 1H), 11.13 (s, 1H); 13C NMR (DMSO-d6) δ 21.94, 30.90, 37.83, 42.51, 48.82, 55.05, 98.34, 107.08, 121.88, 127.12, 131.51, 133.17, 134.61, 138.20, 139.18, 160.28, 166.90, 167.42, 169.77, 170.34, 172.73; Anal. Calcd. for C24H23N3O7: C, 61.93; H, 4.98; N, 9.03. Found: C, 61.62; H, 4.61; N, 8.91.

Workup

  1. stirringThe mixture was stirred at room temperature overnight
  2. concentrationwas then 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)

Sources & evidence

ORD record
ord-f9a5e7a8489f4764a425b6bd04a86e45
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Reaction notes

Loading…