1,8-Diazabicyclo(5.4.0)undec-7-ene → HCID 44132358, compound

HRID 448435Notes

Reaction equation

HRID 448435 reaction equation
[N:1]12[CH2:11]CCN=[C:7]1CCCC[CH2:2]2.Cl.[NH2:13][CH2:14][C:15]1[CH:23]=[CH:22][CH:21]=[C:20]2[C:16]=1[C:17](=[O:33])[N:18]([CH:25]1[CH2:30][CH2:29][C:28](=[O:31])[NH:27][C:26]1=[O:32])[C:19]2=[O:24].ClC(Cl)([O:37]C(=O)OC(Cl)(Cl)Cl)Cl.CNC.C1COCC1>C(#N)C>[O:32]=[C:26]1[CH:25]([N:18]2[C:17](=[O:33])[C:16]3[C:20](=[CH:21][CH:22]=[CH:23][C:15]=3[CH2:14][NH:13][C:2](=[O:37])[N:1]([CH3:11])[CH3:7])[C:19]2=[O:24])[CH2:30][CH2:29][C:28](=[O:31])[NH:27]1

Participants

6

Reactant 4

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 94429TriphosgeneHCID 219885254-(aminomethyl)-2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione hydrochlorideHCID 22320367Dimethylamine tetrahydrofuran

Product 1

HCID 44132358HCID 44132358, compoundYield 101.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

1,8-Diazabicyclo[5,4,0]undec-7-ene (1.0 g, 6.8 mmol) was added to a stirred suspension of 4-aminomethyl-2-(2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dione hydrochloride (1.0 g, 3.1 mmol) in acetonitrile (50 mL). The mixture was stirred for 30 minutes, then added slowly to a stirred solution of triphosgen (0.3 g, 1.1 mmol) in acetonitrile (20 mL) over 20 minutes. After stirring for another 10 minutes, a solution of dimethylamine/THF (2.0 M, 1.6 mL, 3.1 mmol) and diidopropylethylamine (0.5 g, 3.7 mmol) was added in one portion. The mixture was stirred at room temperature overnight. The mixture was concentrated, and the residue was dissolved in methylene chloride (80 mL). The methylene chloride solution was washed with 1N HCl (40 mL), water (40 mL), and brine (40 mL), and dried (MgSO4). Solvent was removed and purified by chromatography (silica gel) to give 3-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-1,1-dimethyl-urea (0.4 g, 36%) as a white solid: mp 143-145° C.; 1H NMR (DMSO-d6) δ 2.04-2.08 (m, 1H), 2.50-2.63 (m, 2H), 2.84 (s, 6H, 2CH3), 2.84-2.96 (m, m, 1H), 4.68 (d, J=5.6 Hz, 2H, CH2), 5.11-5.18 (dd, J=5.2 and 121.5 Hz, 1H, CH), 6.98 (t, J=5.6 Hz, 1H, NH), 7.69-7.85 (m, 3H, Ar), 11.13 (s, 1H, NH); 13C NMR (DMSO-d6) δ 21.98, 30.93, 35.88, 39.30, 48.82, 121.45, 126.75, 131.38, 132.92, 134.56, 141.44, 148.14, 167.06, 167.63, 169.84, 172.75; Anal. calcd. for C17H18N4O5: C, 56.98; H, 5.06; N, 15.63. Found: C, 56.87; H, 5.16; N, 15.16.

Workup

  1. stirringAfter stirring for another 10 minutes
  2. stirringThe mixture was stirred at room temperature overnight
  3. concentrationThe mixture was concentrated
  4. dissolutionthe residue was dissolved in methylene chloride (80 mL)
  5. washThe methylene chloride solution was washed with 1N HCl (40 mL), water (40 mL), and brine (40 mL)
  6. dry with materialdried (MgSO4)
  7. customSolvent was removed
  8. custompurified by chromatography (silica gel)

Sources & evidence

ORD record
ord-79eccbdc639c443a907791316002eea1
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Reaction notes

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