Diisopropylethylamine → 2-(4-(1-(5-Fluoro-2-methylphenyl)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 69383Notes

Reaction equation

HRID 69383 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:30]=[CH:31][C:32]([CH3:39])=[C:33]([CH2:35][C@@H:36]([NH2:38])[CH3:37])[CH:34]=1.C(N(CC)C(C)C)(C)C>C(O)CCC>[F:28][C:29]1[CH:30]=[CH:31][C:32]([CH3:39])=[C:33]([CH2:35][CH:36]([NH:38][C:2]2[CH:7]=[CH:6][NH:5][C:4](=[O:8])[C:3]=2[C:9]2[NH:27][C:12]3=[CH:13][C:14]4[C:15](=[O:26])[N:16]([CH2:21][CH2:22][N:23]([CH3:25])[CH3:24])[C:17](=[O:20])[C:18]=4[CH:19]=[C:11]3[N:10]=2)[CH3:37])[CH:34]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 66687145(2S)-1-(5-fluoro-2-methylphenyl)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 1363406652-(4-(1-(5-Fluoro-2-methylphenyl)propan-2-ylamino)-2-oxo-1,2-dihydropyridin-3-yl)-6-(2-(dimethylamino)ethyl)imidazo[4,5-f]isoindole-5,7(1H,6H)-dioneYield 84.3%

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 (1.05 g, 2.72 mmol), (S)-1-(5-fluoro-2-methylphenyl)propan-2-amine (0.55 g, 3.26 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 bown solid product, 1.18 g, 84.3% yield. MS: 517.2 [M+H]+. 1H NMR (DMSO-d6, 300 MHz): δ 13.42 (s, 1H), 11.23 (s, 1H), 10.86 (d, 1H, J=8.1 Hz), 8.13 (s, 1H), 8.00 (s, 1H), 7.31-7.10 (m, 3H), 6.90-6.83 (m, 1H), 6.14 (d, 1H, J=7.5 Hz), 4.22-4.13 (m, 1H), 3.68 (t, 2H, J=6.5 Hz), 3.00 (d, 2H, J=6.9 Hz), 2.51-2.47 (m, 2H), 2.42 (s, 3H), 2.18 (s, 6H), 1.34 (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 bown solid product, 1.18 g, 84.3% yield

Sources & evidence

ORD record
ord-c0ef1360d9484cacabd96b4103f794ce
Source dataset
uspto-grants-2014_09
Patent number
US08822500B2

Reaction notes

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