Triethylamine → HCID 16117614, compound

HRID 448305Notes

Reaction equation

HRID 448305 reaction equation
C(N(CC)CC)C.Cl.[NH2:9][CH2:10][C:11]1[CH:19]=[CH:18][CH:17]=[C:16]2[C:12]=1[CH2:13][N:14]([CH:21]1[CH2:26][CH2:25][C:24](=[O:27])[NH:23][C:22]1=[O:28])[C:15]2=[O:20].[Cl:29][C:30]1[CH:31]=[C:32]([CH:36]=[CH:37][C:38]=1[Cl:39])[C:33](Cl)=[O:34]>C1COCC1>[Cl:29][C:30]1[CH:31]=[C:32]([CH:36]=[CH:37][C:38]=1[Cl:39])[C:33]([NH:9][CH2:10][C:11]1[CH:19]=[CH:18][CH:17]=[C:16]2[C:12]=1[CH2:13][N:14]([CH:21]1[CH2:26][CH2:25][C:24](=[O:27])[NH:23][C:22]1=[O:28])[C:15]2=[O:20])=[O:34]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 76403Benzoyl chloride, 3,4-dichloro-HCID 219885683-(4-(Aminomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione hydrochloride

Product 1

HCID 16117614HCID 16117614, compoundYield 64%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
5 °C

Procedure

Triethylamine (0.5 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) and 3,4-dichlorobenzoyl chloride (0.6 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 reaction was quenched with methanol (1 mL) and concentrated. The residue was stirred with 1N HCl (40 mL) for 1 hour then filtered. The solid was slurried with hot acetone (25 mL) to give 3,4-dichloro-N-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-benzamide (0.6 g, 62%) as a white solid: mp>260° C.; 1H NMR (DMSO-d6) δ 2.01-2.08 (m, 1H), 2.33-2.65 (m, 2H), 2.86-3.00 (m, 1H), 4.40-4.61 (m, 4H, 2CH2), 5.11-5.19 (dd, J=5.0 and 13.2 Hz, 1H, CH), 7.47-7.88 (m, 5H, Ar), 8.12 (d, J=1.9 Hz, 1H, Ar), 9.26 (t, J=5.6 Hz, 1H, NH), 11.02 (s, 1H, NH); 13C NMR (DMSO-d6) δ 22.56, 31.16, 39.73, 46.25, 51.58, 121.78, 127.60, 128.34, 129.22, 130.73, 130.81, 131.27, 131.65, 134.16, 134.33, 140.23, 164.09, 168.01, 170.98, 172.81; Anal. calcd. for C21H17N3O4Cl2: C, 56.52; H, 3.84; N, 9.42; Cl, 15.89. Found: C, 56.42; H, 3.79; N, 9.21; Cl, 15.85.

Workup

  1. stirringthe mixture was stirred at room temperature overnight
  2. customThe reaction was quenched with methanol (1 mL)
  3. concentrationconcentrated
  4. stirringThe residue was stirred with 1N HCl (40 mL) for 1 hour
  5. filtrationthen filtered

Sources & evidence

ORD record
ord-d78eb241141341d9a6e8136fab8e49bf
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Reaction notes

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