Triethylamine → HCID 58827286, compound

HRID 448452Notes

Reaction equation

HRID 448452 reaction equation
[CH3:1][N:2]1[CH:6]=[CH:5][CH:4]=[C:3]1[C:7]([OH:9])=O.C(C1NC=CN=1)(C1NC=CN=1)=O.C(N(CC)CC)C.Cl.[NH2:30][CH2:31][C:32]1[CH:40]=[CH:39][CH:38]=[C:37]2[C:33]=1[C:34](=[O:50])[N:35]([CH:42]1[CH2:47][CH2:46][C:45](=[O:48])[NH:44][C:43]1=[O:49])[C:36]2=[O:41]>CN(C=O)C>[O:49]=[C:43]1[CH:42]([N:35]2[C:34](=[O:50])[C:33]3[C:37](=[CH:38][CH:39]=[CH:40][C:32]=3[CH2:31][NH:30][C:7]([C:3]3[N:2]([CH3:1])[CH:6]=[CH:5][CH:4]=3)=[O:9])[C:36]2=[O:41])[CH2:47][CH2:46][C:45](=[O:48])[NH:44]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 814531-Methyl-2-pyrrolecarboxylic acidHCID 5250894Bis-(1H-imidazol-2-YL)-methanoneHCID 219885254-(aminomethyl)-2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione hydrochloride

Product 1

HCID 58827286HCID 58827286, compoundYield 25.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 1-methyl-1H-pyrrole-2-carboxylic acid (0.3 g, 2.6 mmol) and carbonyl diimidazole (0.5 g, 3.0 mmol) in DMF (30 mL) was stirred for 2 hours. Triethylamine (0.8 g, 6.0 mmol) was added, followed by 4-aminomethyl-2-(2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dione hydrochloride (0.7 g, 2.0 mmol). The mixture was stirred at 75° C. (oil bath) overnight. The mixture was cooled to room temperature and concentrated. The residue was stirred with EtOAc (80 mL) and water (30 mL). The EtOAc solution was washed with water (2×40 mL) and brine (40 mL), and dried (MgSO4). Solvent was removed, and the residue was purified by chromatography (SiO2, CH2Cl2: CH3OH 97.5:2.5) to give 1-methyl-1H-pyrrole-2-carboxylic acid [2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-amide (0.2 g, 25%) as a white solid: mp>260° C.; 1H NMR (DMSO-d6) δ 2.06-2.10 (m, 1H), 2.50-2.65 (m, 2H), 2.84-2.97 (m, 1H), 3.83 (s, 3H), 4.86 (d, J=5.8 Hz, 2H), 5.13-5.20 (dd, J=5.5 and 12.7 Hz, 1H), 6.04 (t, J=3.4 Hz, 1H), 6.88-6.93 (m, 2H), 7.70-7.86 (m, 3H), 8.63 (t, J=5.8 Hz, 1H), 11.13 (s, 1H); 13C NMR (DMSO-d6) δ 21.98, 30.93, 36.19, 37.47, 48.86, 106.75, 112.63, 121.73, 124.98, 126.95, 128.07, 131.49, 132.96, 134.76, 140.06, 161.56, 166.98, 167.58, 169.82, 172.74; Anal. calcd. for C20H18N4O5+0.18H2O+0.1 ether: C, 60.49; H, 4.82; N, 13.83. Found: C, 60.54; H, 4.74; N, 13.50.

Workup

  1. stirringThe mixture was stirred at 75° C. (oil bath) overnight
  2. concentrationconcentrated
  3. stirringThe residue was stirred with EtOAc (80 mL) and water (30 mL)
  4. washThe EtOAc solution was washed with water (2×40 mL) and brine (40 mL)
  5. dry with materialdried (MgSO4)
  6. customSolvent was removed
  7. customthe residue was purified by chromatography (SiO2, CH2Cl2: CH3OH 97.5:2.5)

Sources & evidence

ORD record
ord-655ec1947423468b8c9c8b6af765e3ba
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Reaction notes

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