Diisopropylethylamine → 2-(4-(1-(2,5-Difluorophenyl)propan-2-ylamino)-2-oxo-1,2-dihydropyridin-3-yl)-6-(2-(dimethylamino)ethyl)imidazo[4,5-f]isoindole-5,7(1H,6H)-dione

HRID 69349Notes

Reaction equation

HRID 69349 reaction equation
Cl[C:2]1[CH:7]=[CH:6][NH:5][C:4](=[O:8])[C:3]=1[C:9]1[NH:27][C:12]2=[CH:13][C:14]3[C:15](=[O:26])[N:16]([CH2:21][CH2:22][N:23]([CH3:25])[CH3:24])[C:17](=[O:20])[C:18]=3[CH:19]=[C:11]2[N:10]=1.[F:28][C:29]1[CH:34]=[CH:33][C:32]([F:35])=[CH:31][C:30]=1[CH2:36][CH:37]([NH2:39])[CH3:38].C(N(CC)C(C)C)(C)C>C(O)CCC>[F:28][C:29]1[CH:34]=[CH:33][C:32]([F:35])=[CH:31][C:30]=1[CH2:36][CH:37]([NH:39][C:2]1[CH:7]=[CH:6][NH:5][C:4](=[O:8])[C:3]=1[C:9]1[NH:27][C:12]2=[CH:13][C:14]3[C:15](=[O:26])[N:16]([CH2:21][CH2:22][N:23]([CH3:25])[CH3:24])[C:17](=[O:20])[C:18]=3[CH:19]=[C:11]2[N:10]=1)[CH3:38]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 433125451-(2,5-Difluorophenyl)propan-2-amineHCID 1363406382-(4-chloro-2-oxo-1,2-dihydropyridin-3-yl)-6-(2-(dimethylamino)ethyl)imidazo[4,5-f]isoindole-5,7(1H,6H)-dione

Product 1

HCID 1363406432-(4-(1-(2,5-Difluorophenyl)propan-2-ylamino)-2-oxo-1,2-dihydropyridin-3-yl)-6-(2-(dimethylamino)ethyl)imidazo[4,5-f]isoindole-5,7(1H,6H)-dioneYield 85.2%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

2-(4-Chloro-2-oxo-1,2-dihydropyridin-3-yl)-6-(2-(dimethylamino)ethyl)imidazo[4,5-f]isoindole-5,7(1H,6H)-dione (1.00 g, 2.59 mmol), 1-(2,5-difluorophenyl)propan-2-amine (0.44 g, 2.59 mmol), n-butanol (50 mL) and N,N-diisopropylethylamine (10 mL) were mixed together in a flask. The reaction mixture was stirred and heated to reflux overnight under argon. Solvents were removed under reduced pressure. The residue solid was purified by column chromatography (silica-gel, CH2Cl2/MeOH=9/1 v/v) to give a brown solid product, 1.15 g, 85.2% yield. MS: 521.2 [M+H]+. 1H NMR (DMSO-d6, 300 MHz): δ 13.43 (s, 1H), 11.31 (d, 1H, J=6.0 Hz), 10.98 (d, 1H, J=7.5 Hz), 8.16 (s, 1H), 8.01 (s, 1H), 7.42-7.35 (m, 2H), 7.20-7.13 (m, 1H), 7.10-7.02 (m, 1H), 6.18 (d, 1H, J=7.2 Hz), 4.16 (m, 1H), 3.95 (t, 2H, J=6.0 Hz), 3.33 (m, 2H), 3.10-2.96 (m, 2H), 2.81 (s, 6H), 1.33 (d, 3H, J=6.3 Hz).

Workup

  1. temperatureheated
  2. temperatureto reflux overnight under argon
  3. customSolvents were removed under reduced pressure
  4. customThe residue solid was purified by column chromatography (silica-gel, CH2Cl2/MeOH=9/1 v/v)
  5. customto give a brown solid product, 1.15 g, 85.2% yield

Sources & evidence

ORD record
ord-2474978802d34693a4eead68b45fd777
Source dataset
uspto-grants-2014_09
Patent number
US08822500B2

Reaction notes

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