Hydrochloric Acid → (S)-6-(6-Fluoropyridin-3-yl)-2-(2-oxo-4-((1-(2,3,5,6-tetrafluorophenyl)propan-2-yl)amino)-1,2-dihydropyridin-3-yl)imidazo[4,5-f]isoindole-5,7(1H,6H)-dione

HRID 920475ノート

反応式

HRID 920475 の反応式
Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([O:8]C)[C:3]=1[C:10]1[NH:30][C:13]2=[CH:14][C:15]3[C:16](=[O:29])[N:17]([C:22]4[CH:23]=[N:24][C:25]([F:28])=[CH:26][CH:27]=4)[C:18](=[O:21])[C:19]=3[CH:20]=[C:12]2[N:11]=1.Cl.[F:32][C:33]1[C:38]([F:39])=[CH:37][C:36]([F:40])=[C:35]([F:41])[C:34]=1[CH2:42][C@@H:43]([NH2:45])[CH3:44].C(N(CC)C(C)C)(C)C>O1CCOCC1.C(O)CCC>[F:28][C:25]1[N:24]=[CH:23][C:22]([N:17]2[C:16](=[O:29])[C:15]3[CH:14]=[C:13]4[NH:30][C:10]([C:3]5[C:4](=[O:8])[NH:5][CH:6]=[CH:7][C:2]=5[NH:45][C@@H:43]([CH3:44])[CH2:42][C:34]5[C:35]([F:41])=[C:36]([F:40])[CH:37]=[C:38]([F:39])[C:33]=5[F:32])=[N:11][C:12]4=[CH:20][C:19]=3[C:18]2=[O:21])=[CH:27][CH:26]=1

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 666867222-(4-Chloro-2-methoxypyridin-3-yl)-6-(6-fluoropyridine-3-yl)imidazo[4,5-f]isoindole-5,7(1H, 6H)-dioneHCID 86663212(2S)-1-(2,3,5,6-Tetrafluorophenyl)propan-2-amine

生成物 1

HCID 136353590(S)-6-(6-Fluoropyridin-3-yl)-2-(2-oxo-4-((1-(2,3,5,6-tetrafluorophenyl)propan-2-yl)amino)-1,2-dihydropyridin-3-yl)imidazo[4,5-f]isoindole-5,7(1H,6H)-dione収率 63%

試薬・触媒・溶媒 2

HCID 2631-Butanol溶媒HCID 312751,4-Dioxane溶媒

実験手順

2-(4-Chloro-2-methoxypyridin-3-yl)-6-(6-fluoropyridine-3-yl)imidazo[4,5-f]isoindole-5,7(1H, 6H)-dione (0.15 g, 0.35 mmol) was dissolved in 10 mL of 1,4-dioxane and 5 mL of concentrated HCl at rt. The reaction mixture was stirred at rt overnight. Then, the volatile was removed to give a yellow-brown solid. This solid was mixed with (S)-1-(2,3,5,6-tetrafluorophenyl)propan-2-amine (55 mg, 0.26 mmol), N,N-diisopropylethylamine (1 mL) and n-butanol (20 mL) in a flask. The reaction mixture was stirred and heated to reflux overnight under argon. Then, volatiles were removed under reduced pressure. The residue solid was purified by column chromatography (silica-gel, CH2Cl2/MeOH=9/1 v/v) to give a yellow-brown solid product, 80 mg, 63.0% yield. MS: 578.8 [M−H]−. 1H NMR (DMSO-d6, 500 MHz): δ 13.48 (s, 1H), 11.35 (d, 1H, J=6.0 Hz), 10.91 (d, 1H, J=8.5 Hz), 8.40 (d, 1H, J=2.0 Hz), 8.26 (s, 1H), 8.18-8.14 (m, 1H), 8.04 (s, 1H), 7.77-7.70 (m, 1H), 7.42-7.39 (m, 2H), 6.19 (d, 1H, J=7.5 Hz), 4.27-4.24 (m, 1H), 3.18-3.10 (m, 2H), 1.39 (d, 3H, J=6.0 Hz).

後処理

  1. customat rt
  2. customThen, the volatile was removed
  3. customto give a yellow-brown solid
  4. stirringThe reaction mixture was stirred
  5. temperatureheated
  6. temperatureto reflux overnight under argon
  7. customThen, volatiles were removed under reduced pressure
  8. customThe residue solid was purified by column chromatography (silica-gel, CH2Cl2/MeOH=9/1 v/v)
  9. customto give a yellow-brown solid product, 80 mg, 63.0% yield

出典と根拠

ORDレコード
ord-59344786d7594d76bed1c8772f9cc06d
出典データセット
uspto-grants-2016_03
特許番号
US09273055B2

反応ノート

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