Hydrochloric Acid → HCID 136405597, compound

HRID 69373Notes

Reaction equation

HRID 69373 reaction equation
Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([O:8]C)[C:3]=1[C:10]1[NH:23][C:13]2=[CH:14][C:15]3[C:16](=[O:22])[NH:17][C:18](=[O:21])[C:19]=3[CH:20]=[C:12]2[N:11]=1.Cl.[F:25][C:26]1[C:31]([F:32])=[CH:30][C:29]([F:33])=[CH:28][C:27]=1[CH2:34][CH:35]([NH2:37])[CH3:36].C(N(CC)[CH:42]([CH3:44])[CH3:43])(C)C>O1CCOCC1.C(O)CCC>[O:8]=[C:4]1[C:3]([C:10]2[NH:11][C:12]3=[CH:20][C:19]4[C:18](=[O:21])[N:17]([CH:42]([CH3:43])[CH2:44][C:27]5[CH:28]=[C:29]([F:33])[CH:30]=[C:31]([F:32])[C:26]=5[F:25])[C:16](=[O:22])[C:15]=4[CH:14]=[C:13]3[N:23]=2)=[C:2]([NH:37][CH:35]([CH3:36])[CH2:34][C:27]2[CH:28]=[C:29]([F:33])[CH:30]=[C:31]([F:32])[C:26]=2[F:25])[CH:7]=[CH:6][NH:5]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 55253634HCID 55253634, compoundHCID 66687188HCID 66687188, compound

Product 1

HCID 136405597HCID 136405597, compoundYield 76.5%

Reagents, catalysts & solvents 2

HCID 2631-ButanolSolventHCID 312751,4-DioxaneSolvent

Procedure

2-(4-Chloro-2-methoxypyridin-3-yl)imidazo[4,5-f]isoindole-5,7(1H, 6H)-dione (0.522 g, 1.59 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 1-(2,3,5-trifluorophenyl)propan-2-amine (0.30 g, 1.59 mmol), N,N-diisopropylethylamine (1.10 g, 9.54 mmol) 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, 0.78 g, 76.5% yield. MS: 640.2 [M+H]+. 1H NMR (DMSO-d6, 500 MHz): δ 13.38 (s, 1H), 11.32-11.29 (m, 1H), 10.94-10.91 (m, 1H), 8.06 (s, 1H), 7.84 (s, 1H), 7.64-7.60 (m, 1H), 7.37-7.34 (m, 1H), 7.08-6.99 (m, 2H), 6.14 (d, 1H, J=7.5 Hz), 4.50 (m, 1H), 4.18 (m, 1H), 3.37-3.32 (m, 1H), 3.15-3.01 (m, 3H), 1.57 (d, 3H, J=7.0 Hz), 1.35 (d, 3H, J=6.5 Hz).

Workup

  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, 0.78 g, 76.5% yield

Sources & evidence

ORD record
ord-5915b2a9588d4bb48c297a559da96c5f
Source dataset
uspto-grants-2014_09
Patent number
US08822500B2

Reaction notes

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