Potassium Iodide → HCID 69294583, compound

HRID 899828Notes

Reaction equation

HRID 899828 reaction equation
[N:1]1[C:10]2[CH:9]([NH:11][CH2:12][CH2:13][CH2:14][CH2:15][N:16]3[C:24](=[O:25])[C:23]4[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=4)[C:17]3=[O:26])[CH2:8][CH2:7][CH2:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.C(N(C(C)C)CC)(C)C.[I-].[K+].Cl[CH2:39][C:40]1[NH:44][C:43]2[C:45]([F:49])=[CH:46][CH:47]=[CH:48][C:42]=2[N:41]=1>C(#N)C>[F:49][C:45]1[C:43]2[N:44]=[C:40]([CH2:39][N:11]([CH:9]3[C:10]4[N:1]=[CH:2][CH:3]=[CH:4][C:5]=4[CH2:6][CH2:7][CH2:8]3)[CH2:12][CH2:13][CH2:14][CH2:15][N:16]3[C:24](=[O:25])[C:23]4[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=4)[C:17]3=[O:26])[NH:41][C:42]=2[CH:48]=[CH:47][CH:46]=1

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 81531DiisopropylethylamineHCID 589971372-[4-(5,6,7,8-Tetrahydroquinolin-8-ylamino)-butyl]-isoindole-1,3-dioneHCID 178505552HCID 178505552, compound

Product 1

HCID 69294583HCID 69294583, compoundYield 41%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

To a stirred solution of 2-[4-(5,6,7,8-tetrahydro-quinolin-8-ylamino)-butyl]-isoindole-1,3-dione (146 mg, 0.418 mmol), diisopropylethylamine (0.15 mL, 0.861 mmol) and potassium iodide (14 mg, 0.084 mmol) in acetonitrile (2.5 mL) was added 2-chloromethyl-7-fluoro-1H-benzimidazole (prepared according to the procedures described in Bridger et al. U.S. Provisional Application 60/232,891 filed 15 Sep. 2000 and from Application 60/234,510 filed 22 Sep. 2000) (80 mg, 0.433 mmol) and the mixture heated at 60° C. for 18 hours. The mixture was then concentrated and the residue diluted with CH2Cl2 (30 mL). The solution was washed with brine (3×15 mL). The combined aqueous phase was extracted with CH2Cl2 (1×15 mL). The combined organic phase was dried (Na2SO4), filtered and concentrated under reduced pressure to give a crude brown foam. The foam was purified by flash chromatography (1.75 cm ID, 12 g silica, 50:1:1 CH2Cl2: MeOH: NH4OH) to give pure 2-{4-[(4-fluoro-1H-benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-butyl}-isoindole-1,3-dione (86 mg, 41%). 1H NMR (CDCl3) δ 1.33-1.76 (m, 5H), 1.85-2.10 (m, 3H), 2.14-2.25 (m, 1H), 2.54-2919 (m, 4H), 3.45-3.55 (m, 2H), 3.98-4.24 (m, 3H), 7.29-7.45 (m, 2H), 7.63-7.69 (m, 2H), 7.72-7.77 (m, 2H), 8.56-8.63 (m, 1H).

Workup

  1. customprepared
  2. concentrationThe mixture was then concentrated
  3. additionthe residue diluted with CH2Cl2 (30 mL)
  4. washThe solution was washed with brine (3×15 mL)
  5. extractionThe combined aqueous phase was extracted with CH2Cl2 (1×15 mL)
  6. dry with materialThe combined organic phase was dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto give a crude brown foam
  10. customThe foam was purified by flash chromatography (1.75 cm ID, 12 g silica, 50:1:1 CH2Cl2: MeOH: NH4OH)

Sources & evidence

ORD record
ord-6b7740bc845f42f2ab5edd350d30f544
Source dataset
uspto-grants-2008_04
Patent number
US07354934B2

Reaction notes

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