Triethylamine → HCID 16117207, compound

HRID 448285Notes

Reaction equation

HRID 448285 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]([C:24]1[CH:25]=[C:26]([CH:30]=[CH:31][CH:32]=1)[C:27](Cl)=[O:28])#[N:23].C(N(CC)CC)C>C1COCC1>[C:22]([C:24]1[CH:25]=[C:26]([CH:30]=[CH:31][CH:32]=1)[C:27]([NH: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])=[O:28])#[N:23]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 3084833-Cyanobenzoyl chlorideHCID 219885683-(4-(Aminomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione hydrochloride

Product 1

HCID 16117207HCID 16117207, compoundYield 94.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
5 °C

Procedure

A 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-cyanobenzoyl chloride (0.4 g, 2.5 mmol) in THF (30 mL) was cooled to 5° C. Triethylamine (0.5 g, 4.8 mmol) was added, and the mixture was stirred at room temperature for 5 hours. The mixture was concentrated, and the residue was stirred with 1N HCl (40 mL). The mixture was filtered, and the solid was slurried with warmed ethanol (20 mL) to give 3-cyano-N-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-benzamide (0.8 g, 92%) as a white solid: mp 282-284° C.; 1H NMR (DMSO-d6) δ 2.01-2.06 (m, 1H), 2.34-2.65 (m, 2H), 2.86-3.00 (m, 1H), 4.41-4.62 (m, 4H, 2CH2), 5.11-5.18 (dd, J=4.8 and 13 Hz, 1H, CH), 7.48-7.74 (m, 4H, Ar), 8.01 (d, J=7.7 Ha, 1H, Ar), 8.17 (d, J=7.9 Hz, 1H, Ar), 8.31 (s, 1H, Ar), 9.28 (t, J=5.0 Hz, 1H, NH), 11.01 (s, 1H, NH); 13C NMR (DMSO-d6) δ 22.69, 31.17, 46.26, 51.60, 111.50, 118.26, 121.79, 128.35, 129.80, 130.82, 130.89, 131.65, 132.08, 134.14, 134.79, 135.00, 140.25, 164.54, 168.02, 170.98, 172.81; Anal. calcd. for C22H18N4O4: C, 65.67; H, 4.51; N, 13.92. Found: C, 65.38; H, 4.42; N, 13.77.

Workup

  1. concentrationThe mixture was concentrated
  2. stirringthe residue was stirred with 1N HCl (40 mL)
  3. filtrationThe mixture was filtered

Sources & evidence

ORD record
ord-3d2f4aa9b31c42339ebb6fbb2127ff43
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Reaction notes

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