Triethylamine → HCID 66883417, compound

HRID 915373Notes

Reaction equation

HRID 915373 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:7](=O)[CH2:8][C:9]2[CH:26]=[CH:25][CH:24]=[C:23]([Cl:27])[C:10]=2[C:11]([NH:13][CH2:14][C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:16]=2[F:22])=[O:12])[O:5][CH:6]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.CCN(CC)CC>O1CCOCC1>[Br:1][C:2]1[CH:3]=[C:4]([C:7]2[N:13]([CH2:14][C:15]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:16]=3[F:22])[C:11](=[O:12])[C:10]3[C:9]([CH:8]=2)=[CH:26][CH:25]=[CH:24][C:23]=3[Cl:27])[O:5][CH:6]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 521998p-Toluenesulfonic acid monohydrateHCID 66884190HCID 66884190, compound

Product 1

HCID 66883417HCID 66883417, compoundYield 82.7%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a solution of 2-[2-(4-bromofuran-2-yl)-2-oxoethyl]-6-chloro-N-(2,4-difluorobenzyl)benzamide (2.4 g, 5.1 mmol), prepared in a manner similar to that described above in Paragraph B, in dioxane (30 mL) was added 4-toluenesulfonic acid monohydrate (450 mg, 2.4 mmol). The resulting solution was heated to reflux. After 20 hours at reflux the reaction solution was allowed to cool to ambient temperature, and treated with Et3N (2.0 mL, 14 mmol). The crude product was purified by adsorbing the material onto silica gel from the reaction solution, loading the resulting solid onto the column and eluting with a gradient from 10% to 50% EtOAc in hexane containing 10% CH2Cl2 (to improve the solubility of the product). The broad peak that eluted was collected to afford 3-(4-bromofuran-2-yl)-8-chloro-2-(2,4-difluorobenzyl)-2H-isoquinolin-1-one (1.9 g, 82% yield) as a brown powder. 1H-NMR (400 MHz, CDCl3): δ 7.56-7.51 (2H, m), 7.47 (1H, d, J=0.8 Hz), 7.43 (1H, dd, J=6.3, 2.8 Hz), 7.06-6.99 (1H, m), 6.79-6.73 (2H, m), 6.68 (1H, s), 6.49 (1H, d, J=0.8 Hz), 5.32 (2H, s).

Workup

  1. temperatureThe resulting solution was heated to reflux
  2. temperatureAfter 20 hours at reflux the reaction solution
  3. customThe crude product was purified
  4. washeluting with a gradient from 10% to 50% EtOAc in hexane containing 10% CH2Cl2 (
  5. washThe broad peak that eluted
  6. customwas collected

Sources & evidence

ORD record
ord-d24de849f51f49458f8a6a040ad74109
Source dataset
uspto-grants-2007_09
Patent number
US07265131B2

Reaction notes

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