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 69348노트

반응식

HRID 69348 반응식
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

참가 물질

7

반응물 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

생성물 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)-dione수율 63%

시약·촉매·용매 2

HCID 2631-Butanol용매HCID 312751,4-Dioxane용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-38066c0e196c4c9f9792bfe1bac13512
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08822500B2

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