3-Methylbenzoyl chloride → HCID 16117346, compound

HRID 448296Notes

Reaction equation

HRID 448296 reaction equation
Cl.[NH2:2][CH2:3][C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[CH2:6][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].[C:22]1([CH3:31])[CH:27]=[CH:26][CH:25]=[C:24]([C:28](Cl)=[O:29])[CH:23]=1>C1COCC1>[O:21]=[C:15]1[CH:14]([N:7]2[CH2:6][C:5]3[C:9](=[CH:10][CH:11]=[CH:12][C:4]=3[CH2:3][NH:2][C:28](=[O:29])[C:24]3[CH:25]=[CH:26][CH:27]=[C:22]([CH3:31])[CH:23]=3)[C:8]2=[O:13])[CH2:19][CH2:18][C:17](=[O:20])[NH:16]1

Participants

4

Reactant 2

HCID 743753-Methylbenzoyl chlorideHCID 219885683-(4-(Aminomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione hydrochloride

Product 1

HCID 16117346HCID 16117346, compoundYield 86%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
5 °C

Procedure

Teiethylamine (0.5 g, 5.2 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) and m-toluoyl chloride (0.5 g, 2.9 mmol) in THF (30 mL) at 5-10° C. After stirring at 5° C. for 10 minutes, the mixture was stirred at room temperature overnight. The mixture was concentrated, and the residue was stirred with 1N HCl (20 mL). The mixture was filtered, and the solid was slurried with hot methanol (15 mL) to give N-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-3-methyl-benzamide (0.7 g, 86%) as a white solid: mp 253-255° C.; 1H NMR (DMSO-d6) δ 2.01-2.05 (m, 1H), 2.35 (s, 3H, CH3), 2.35-2.65 (m, 2H), 2.86-3.00 (m, 1H), 4.40-4.61 (m, 4H, 2CH2), 5.12-5.19 (dd, J=5.0 and 13.2 Hz, 1H, CH), 7.34-7.70 (m, 7H, Ar), 9.05 (t, J=5.6 Hz, 1H, NH), 11.03 (s, 1H, NH); 13C NMR (DMSO-d6) δ 20.90, 22.59, 31.17, 46.28, 51.58, 121.62, 124.36, 127.76, 128.20, 128.30, 130.66, 131.60, 131.86, 134.07, 134.75, 137.59, 140.11, 166.45, 168.06, 170.99, 172.82; Anal. calcd. for C22H21N3O4: C, 67.51; H, 5.41; N, 10.74. Found: C, 67.52; H, 5.35; N, 10.71.

Workup

  1. stirringthe mixture was stirred at room temperature overnight
  2. concentrationThe mixture was concentrated
  3. stirringthe residue was stirred with 1N HCl (20 mL)
  4. filtrationThe mixture was filtered

Sources & evidence

ORD record
ord-9c20f3995c904e589021db6a34e3bc2c
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Reaction notes

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