Triethylamine → 6-(3-Ethoxy-4-Methoxyphenyl)Pyridine-2-Carboxylic Acid [2-(2,6-Dioxopiperidin-3-yl)-1,3-Dioxo-2,3-Dihydro-1H-Isoindol-4-yl-Methyl]Amide

HRID 448449Notes

Reaction equation

HRID 448449 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([OH:20])=O)C=2)[CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[CH3:2].C1N=C[N:23](C(N2C=NC=C2)=O)C=1.Cl.[NH2:34][CH2:35][C:36]1[CH:44]=[CH:43][CH:42]=[C:41]2[C:37]=1[C:38](=[O:54])[N:39]([CH:46]1[CH2:51][CH2:50][C:49](=[O:52])[NH:48][C:47]1=[O:53])[C:40]2=[O:45].C(N(CC)CC)C>CN(C=O)C.O>[O:53]=[C:47]1[CH:46]([N:39]2[C:38](=[O:54])[C:37]3[C:41](=[CH:42][CH:43]=[CH:44][C:36]=3[CH2:35][NH:34][C:18]([C:14]3[CH:15]=[CH:16][CH:17]=[C:12]([C:6]4[CH:7]=[CH:8][C:9]([O:10][CH3:11])=[C:4]([O:3][CH2:1][CH3:2])[CH:5]=4)[N:23]=3)=[O:20])[C:40]2=[O:45])[CH2:51][CH2:50][C:49](=[O:52])[NH:48]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 219885254-(aminomethyl)-2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione hydrochlorideHCID 583071913'-Ethoxy-4'-Methoxybiphenyl-3-Carboxylic Acid

Product 1

HCID 588273186-(3-Ethoxy-4-Methoxyphenyl)Pyridine-2-Carboxylic Acid [2-(2,6-Dioxopiperidin-3-yl)-1,3-Dioxo-2,3-Dihydro-1H-Isoindol-4-yl-Methyl]AmideYield 69.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 3′-ethoxy-4′-methoxybiphenyl-3-carboxylic acid (0.55 g, 2.0 mmol) and CDI (0.39 g, 2.4 mmol) in DMF (30 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 3 hours. The mixture was poured into water (200 mL) and extracted with ethyl acetate (3×100 mL). The combined organic phases were washed with water (3×150 mL), dried (MgSO4), and evaporated, providing 0.75 g of the product as a pale yellow solid (69% yield): mp 196-198° C.; 1H NMR (DMSO-d6) δ 1.36 (t, J=6.9 Hz, 3H), 2.05-2.10 (m, 1H), 2.54-2.64 (m, 2H), 2.85-2.98 (m, 1H), 3.83 (s, 3H), 4.18 (q, J=6.3 Hz, 2H), 5.02 (d, J=6.3 Hz, 2H), 5.20 (dd, J=12.7 Hz, d=5.4 Hz, 1H), 7.06 (d, J=8.5 Hz, 1H), 7.74-7.83 (m, 4H), 7.87-7.94 (m, 2H), 8.03 (t, J=7.8 Hz, 1H), 8.16 (d, J=7.7 Hz, 1H), 9.56 (t, J=6.3 Hz, 1H), 11.18 (s, 1H); 13C NMR (DMSO-d6) δ 14.8, 22.0, 31.0, 38.6, 49.0, 55.5, 64.0, 111.8, 119.8, 120.0, 122.0, 122.4, 127.3, 130.1, 131.7, 133.3, 134.9, 138.6, 139.1, 148.2, 149.2, 150.5, 155.1, 164.5, 167.0, 167.8, 169.8, 172.7; Anal. calcd for C29H26N4O7.0.5H2O: C, 63.15; H, 4.93; N, 10.16. Found: C, 63.36; H, 4.80; N, 10.19.

Workup

  1. stirringto stir for 3 hours
  2. extractionextracted with ethyl acetate (3×100 mL)
  3. washThe combined organic phases were washed with water (3×150 mL)
  4. dry with materialdried (MgSO4)
  5. customevaporated

Sources & evidence

ORD record
ord-cead14390d544fb49887e9a3551f3118
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Reaction notes

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