Triethylamine → 2,5-Dichloro-N-[2-(2,6-dioxopiperidin-3-YL)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]nicotinamide

HRID 448446

Reaction equation

HRID 448446 reaction equation
Cl.[NH2:2][CH2:3][C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[C:6](=[O:22])[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].[Cl:23][C:24]1[C:29]([C:30](Cl)=[O:31])=[CH:28][C:27]([Cl:33])=[CH:26][N:25]=1.C(N(CC)CC)C>C1COCC1>[Cl:23][C:24]1[N:25]=[CH:26][C:27]([Cl:33])=[CH:28][C:29]=1[C:30]([NH:2][CH2:3][C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[C:6](=[O:22])[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:31]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 27999962,5-Dichloro-nicotinoyl chlorideHCID 219885254-(aminomethyl)-2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione hydrochloride

Product 1

HCID 588272942,5-Dichloro-N-[2-(2,6-dioxopiperidin-3-YL)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]nicotinamideYield 54.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 4-aminomethyl-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione hydrochloride (0.65 g, 2.0 mmol), 2,5-dichloropyridine-3-carbonyl chloride (0.42 g, 2.0 mmol) and triethylamine (0.61 g, 6.0 mmol) in THF (30 mL) was stirred at ambient temperature under nitrogen for 18 hours. The mixture was evaporated, and the residue was chromatographed using a methylene chloride-methanol gradient, eluting with 95:5 methylene chloride-methanol, providing 0.50 g of the product (54% yield): mp>260° C.; 1H NMR (DMSO-d6) δ 2.05-2.09 (m, 1H), 2.53-2.58 (m, 2H), 2.83-2.97 (m, 1H), 4.93 (d, J=5.7 Hz, 2H), 5.17 (dd, J=12.5 Hz, d=5.3 Hz, 1H), 7.82-7.91 (m, 3H), 8.28 (d, J=2.5 Hz, 1H), 8.61 (d, J=2.5 Hz, 1H), 9.35 (t, J=5.7 Hz, 1H), 11.15 (s, 1H); 13C NMR (DMSO-d6) δ 22.0, 30.9, 38.3, 48.9, 122.1, 127.3, 130.3, 131.6, 133.4, 134.9, 137.8, 138.0, 145.0, 148.8, 164.1, 166.9, 167.5, 169.8, 172.8; Anal. calcd for C20H14Cl2N4O5.0.2H2O: C, 51.68; H, 3.12; N, 12.05. Found: C, 51.64; H, 3.05; N, 11.98.

Workup

  1. customThe mixture was evaporated
  2. customthe residue was chromatographed
  3. washeluting with 95:5 methylene chloride-methanol

Sources & evidence

ORD record
ord-c9f3b6e06413422babd0d9b1b45c254e
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Linked notes

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