Butyryl chloride → n-[2-(2,6-Dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1h-isoindol-4-ylmethyl]-butyramide

HRID 448280

Reaction equation

HRID 448280 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].[CH3:33][CH2:34][CH2:35][C:36](Cl)=[O:37]>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:36](=[O:37])[CH2:35][CH2:34][CH3:33])[C:19]2=[O:24])[CH2:30][CH2:29][C:28](=[O:31])[NH:27]1

Participants

5

Reactant 3

HCID 8855Butyryl 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 16117079n-[2-(2,6-Dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1h-isoindol-4-ylmethyl]-butyramideYield 69.3%

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. n-Butyryl chloride (0.3 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 2NHCl (30 mL). Solid was collected and slurried with ethanol (20 mL) to give N-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-butyramide (0.5 g, 67%) as a white solid: mp 244-246° C.; 1H NMR (DMSO-d6) δ 0.85 (t, J=7.4 Hz, 3H, CH3), 1.40-1.60 (m, 2H), 1.99-2.14 (m, 3H), 2.34-2.65 (m, 2H), 2.86-2.98 (m, 1H), 4.32-4.53 (m, 4H), 5.11-5.18 (dd, J=4.9 and 13.2 Hz, 1H, CH), 7.48-7.64 (m, 3H, Ar), 8.13 (t, J=5.1 Hz, 1H, NH), 11.02 (s, 1H, NH); 13C NMR (DMSO-d6) δ 13.67; 18.65, 22.61, 31.19, 37.16, 38.93, 46.15, 51.54, 121.62, 128.29, 130.60, 131.63, 134.82, 140.08, 168.08, 171.02, 172.01, 172.88; Anal. calcd. for C18H21N3O4: C, 62.96; H, 6.16; N, 12.24. Found: C, 63.08; H, 6.06; N, 12.08.

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 2NHCl (30 mL)
  4. customSolid was collected

Sources & evidence

ORD record
ord-31feac5f26d14367b19f07aa86ebb4b3
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Linked notes

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