Benzoyl chloride → N-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-benzamide

HRID 448278

Reaction equation

HRID 448278 reaction equation
N12CCCN=C1CCCCC2.Cl.[NH2:13][CH2:14][C:15]1[CH:23]=[CH:22][CH:21]=[C:20]2[C:16]=1[CH2:17][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].[C:33](Cl)(=[O:40])[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1>C(#N)C>[O:32]=[C:26]1[CH:25]([N:18]2[CH2:17][C:16]3[C:20](=[CH:21][CH:22]=[CH:23][C:15]=3[CH2:14][NH:13][C:33](=[O:40])[C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[C:19]2=[O:24])[CH2:30][CH2:29][C:28](=[O:31])[NH:27]1

Participants

5

Reactant 3

HCID 7412Benzoyl chlorideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 219885683-(4-(Aminomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione hydrochloride

Product 1

HCID 16116956N-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-benzamideYield 68%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

1,8-Diazabicyclo[5,4,0]-undec-7-ene (0.8 g, 5.3 mmol) was added to a stirred suspension of 3-(4-aminomethyl-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione hydrochloride (0.7 g, 2.1 mmol) in acetonitrile (100 mL). The mixture was stirred for 30 minutes, and benzoyl chloride (0.4 g, 3.2 mmol) was added. The mixture was stirred at room temperature overnight. The mixture was concentrated and the residue was stirred with 2N HCl (30 mL) and CH2Cl2 (80 mL). The solid was collected to give N-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-benzamide (0.5 g, 68%) as a white solid: mp 228-230° C.; 1H NMR (DMSO-d6) δ 2.01-2.05 (m, 1H), 2.33-2.65 (m, 2H), 2.86-3.00 (m, 1H), 4.48 (d, J=17.3 Hz, 1H), 4.53 (d, J=22.1 Hz, 1H), 4.55 (s, 2H), 5.12-5.19 (dd, J=5.0 and 13.2 Hz, 1H, CH), 7.44-7.65 (m, 6H, Ar), 7.87 (d, J=7.1 Hz, 2H, Ar), 9.11 (t, J=5.7 Hz, 1H, NH), 11.03 (s, 1H, NH); 13C NMR (DMSO-d6) δ 22.61, 31.20, 46.30, 51.60, 121.67, 127.25, 128.35, 130.67, 131.36, 131.63, 134.07, 134.74, 140.16, 166.37, 168.10, 171.04, 172.88; Anal. calcd. for C21H19N3O4: C, 66.83; H, 5.07; N, 11.13. Found: C, 66.58; H, 5.08; N, 11.12.

Workup

  1. stirringThe mixture was stirred at room temperature overnight
  2. concentrationThe mixture was concentrated
  3. stirringthe residue was stirred with 2N HCl (30 mL) and CH2Cl2 (80 mL)
  4. customThe solid was collected

Sources & evidence

ORD record
ord-b7cb97faa81a4112b25f81532eed2e92
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Linked notes

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