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

HRID 920520Notes

Reaction equation

HRID 920520 reaction equation
Cl[C:2]1[CH:7]=[CH:6][NH:5][C:4](=[O:8])[C:3]=1[C:9]1[NH:29][C:12]2=[CH:13][C:14]3[C:15](=[O:28])[N:16]([CH:21]4[CH2:26][CH2:25][N:24]([CH3:27])[CH2:23][CH2:22]4)[C:17](=[O:20])[C:18]=3[CH:19]=[C:11]2[N:10]=1.[F:30][C:31]1[CH:36]=[CH:35][C:34]([F:37])=[CH:33][C:32]=1[CH2:38][CH:39]([NH2:41])[CH3:40].C(N(CC)C(C)C)(C)C>C(O)CCC>[F:30][C:31]1[CH:36]=[CH:35][C:34]([F:37])=[CH:33][C:32]=1[CH2:38][CH:39]([NH:41][C:2]1[CH:7]=[CH:6][NH:5][C:4](=[O:8])[C:3]=1[C:9]1[NH:29][C:12]2=[CH:13][C:14]3[C:15](=[O:28])[N:16]([CH:21]4[CH2:26][CH2:25][N:24]([CH3:27])[CH2:23][CH2:22]4)[C:17](=[O:20])[C:18]=3[CH:19]=[C:11]2[N:10]=1)[CH3:40]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 433125451-(2,5-Difluorophenyl)propan-2-amineHCID 1362002202-(4-Chloro-2-oxo-1,2-dihydropyridin-3-yl)-6-(1-methylpiperidin-4-yl)-imidazo[4,5-f]isoindole-5,7(1H,6H)-dione

Product 1

HCID 1363406422-(4-((1-(2,5-Difluorophenyl)propan-2-yl)amino)-2-oxo-1,2-dihydropyridin-3-yl)-6-(1-methylpiperidin-4-yl)imidazo[4,5-f]isoindole-5,7(1H,6H)-dioneYield 83.8%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

2-(4-Chloro-2-oxo-1,2-dihydropyridin-3-yl)-6-(1-methylpiperidin-4-yl)-imidazo[4,5-f]isoindole-5,7(1H,6H)-dione (0.59 g, 1.43 mmol), 1-(2,5-difluorophenyl)propan-2-amine (0.29 g, 1.72 mmol), n-butanol (50 mL) and N,N-diisopropylethylamine (5 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, 0.65 g, 83.8% yield. MS: 540.8 [M−H]−. 1H-NMR (DMSO-d6, 300 MHz): δ 13.42 (s, 1H), 11.26 (s, 1 Hz), 10.86 (d, 1H, J=8.0 Hz), 8.12 (s, 1H), 8.01 (s, 1H), 7.32-7.31 (m, 1H), 7.24-7.21 (m, 1H), 7.13-7.11 (m, 1H), 6.88-6.84 (m, 1H), 6.14 (d, 1H, J=7.5 Hz), 4.19-4.14 (m, 2H), 3.37-3.33 (m, 3H), 3.15 (m, 2H), 3.01-2.99 (m, 2H), 2.49 (s, 3H), 2.34 (s, 3H), 1.78-1.77 (m, 2H), 1.33 (d, 3H, J=6.5 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, 0.65 g, 83.8% yield

Sources & evidence

ORD record
ord-0473e7086b3c41f98ee36f53bed0f657
Source dataset
uspto-grants-2016_03
Patent number
US09273055B2

Reaction notes

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