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

HRID 448281Notes

Reaction equation

HRID 448281 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].[Cl:33][C:34]1[CH:35]=[C:36]([CH:40]=[CH:41][CH:42]=1)[C:37](Cl)=[O:38]>C(#N)C>[Cl:33][C:34]1[CH:35]=[C:36]([CH:40]=[CH:41][CH:42]=1)[C:37]([NH: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])=[O:38]

Participants

5

Reactant 3

HCID 69252Benzoyl chloride, 3-chloro-HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 219885683-(4-(Aminomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione hydrochloride

Product 1

HCID 161170803-chloro-N-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-benzamideYield 96%

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 in acetonitrile (100 mL). The mixture was stirred for 30 minutes. 3-Chlorobenzoyl chloride (0.6 g, 3.2 mmol) was added, and the mixture was stirred at room temperature overnight. The mixture was concentrated and the residue was stirred with CH2Cl2 (60 mL) and 2N HCl (30 mL). The mixture was filtered and the solid was slurried with ethanol (20 mL) to give 3-chloro-N-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-benzamide (0.8 g, 96%) as a white solid: mp 266-268° C.; 1H NMR (DMSO-d6) δ 2.01-2.06 (m, 1H), 2.37-2.66 (m, 2H), 2.86-2.99 (m, 1H), 4.48 (d, J=17.3 Hz, 1H), 4.53 (d, J=21.1 Hz, 1H), 4.55 (s, 2H), 5.12-5.20 (dd, J=5.0 and 13.2 Hz, 1H, CH), 7.48-7.66 (m, 5H, Ar), 7.87 (d, J=7.7 Hz, 1H, Ar), 7.93 (d, J=1.3 Hz, 1H, Ar), 9.23 (t, J=5.6 Hz, 1H, NH), 11.03 (s, 1H, NH); 13C NMR (DMSO-d6) δ 22.60, 31.20, 39.66, 46.28, 51.60, 121.76, 126.07, 127.08, 128.38, 130.40, 130.77, 131.22, 131.65, 133.23, 134.37, 136.01, 140.21, 164.94, 168.07, 171.04, 172.88; Anal. calcd. for C21H18N3O4Cl: C, 61.24; H, 4.41; N, 10.20; Cl, 8.61. Found: C, 60.92; H, 4.21; N, 10.01; Cl, 8.92.

Workup

  1. stirringthe mixture was stirred at room temperature overnight
  2. concentrationThe mixture was concentrated
  3. stirringthe residue was stirred with CH2Cl2 (60 mL) and 2N HCl (30 mL)
  4. filtrationThe mixture was filtered

Sources & evidence

ORD record
ord-8afb1d555ea04395b8d7141c1552b1fa
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Reaction notes

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