Triethylamine → Quinoxaline-2-carboxylic acid [2-(2,6-dioxopiperidin-3-YL)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]amide

HRID 448444Notes

Reaction equation

HRID 448444 reaction equation
[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=[CH:3][C:2]=1[C:11]([OH:13])=O.C1N=CN(C(N2C=NC=C2)=O)C=1.Cl.[NH2:27][CH2:28][C:29]1[CH:37]=[CH:36][CH:35]=[C:34]2[C:30]=1[C:31](=[O:47])[N:32]([CH:39]1[CH2:44][CH2:43][C:42](=[O:45])[NH:41][C:40]1=[O:46])[C:33]2=[O:38].C(N(CC)CC)C>CN(C=O)C.O>[O:46]=[C:40]1[CH:39]([N:32]2[C:31](=[O:47])[C:30]3[C:34](=[CH:35][CH:36]=[CH:37][C:29]=3[CH2:28][NH:27][C:11]([C:2]3[CH:3]=[N:4][C:5]4[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=4)[N:1]=3)=[O:13])[C:33]2=[O:38])[CH2:44][CH2:43][C:42](=[O:45])[NH:41]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 96695Quinoxaline-2-carboxylic acidHCID 219885254-(aminomethyl)-2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione hydrochloride

Product 1

HCID 58827342Quinoxaline-2-carboxylic acid [2-(2,6-dioxopiperidin-3-YL)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]amideYield 69%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 2-quinoxalinecarboxylic acid (0.35 g, 2.0 mmol) and CDI (0.39 g, 2.4 mmol) in DMF (25 mL) was stirred at ambient temperature under nitrogen for 90 minutes. 4-Aminomethyl-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione hydrochloride (0.65 g, 2.0 mmol) and triethylamine (0.61 g, 6.0 mmol) were added, and the mixture was allowed to stir for 16 hours. The mixture was poured into water, resulting in precipitation of the product, which was filtered, washed with additional water (40 mL) and dried, providing 0.61 g, in 69% yield: mp>260° C.; 1H NMR (DMSO-d6) δ 2.07-2.12 (m, 1H), 2.56-2.65 (m, 2H), 2.85-2.98 (m, 1H), 5.05 (d, J=6.3 Hz, 2H), 5.19 (dd, J=12.6 Hz, d=5.4 Hz, 1H), 7.78-7.83 (m, 3H), 7.98-8.04 (m, 2H), 8.19-8.24 (m, 2H), 9.50 (s, 1H), 9.76 (t, J=6.3 Hz, 1H), 11.16 (s, 1H); 13C NMR (DMSO-d6) δ 22.0, 30.9, 38.4, 48.9, 121.9, 127.2, 129.1, 129.4, 131.3, 131.6, 132.0, 133.1, 134.8, 138.7, 139.8, 143.0, 143.8, 144.1, 163.7, 167.0, 167.6, 169.8, 172.8; Anal. calcd for C23H17N5O5.0.5H2O: C, 61.06; H, 4.01; N, 15.47. Found: C, 61.19; H, 3.95; N, 15.37.

Workup

  1. stirringto stir for 16 hours
  2. customresulting in precipitation of the product, which
  3. filtrationwas filtered
  4. washwashed with additional water (40 mL)
  5. customdried
  6. customproviding 0.61 g

Sources & evidence

ORD record
ord-aa3bcb3c0ce24c8e8912b810e6a35ea3
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Reaction notes

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