Water → HCID 89783869, compound

HRID 1056057Notes

Reaction equation

HRID 1056057 reaction equation
[Cl:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[C:5]([C:13](=O)[CH3:14])[C:6]([F:12])=[CH:7][CH:8]=2)[N:3]=1.C[CH2:17][N:18](CC)CC.[Si](OS(C(F)(F)F)(=O)=O)(C(C)(C)C)(C)C.O.[CH2:39]1[C:44](=[O:45])[N:43](Br)[C:41](=O)[CH2:40]1.C([O-])(=O)C.[NH4+].N1CCC(=O)CC1=O>C(Cl)Cl.CCO>[Cl:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[C:5]([C:13]3[NH:18][C:17]4[CH2:40][CH2:41][NH:43][C:44](=[O:45])[C:39]=4[CH:14]=3)[C:6]([F:12])=[CH:7][CH:8]=2)[N:3]=1

Participants

10

Reactant 7

HCID 962WaterHCID 8471TriethylamineHCID 67184N-bromobutanimideHCID 123564tert-Butyldimethylsilyl trifluoromethanesulphonateHCID 517165Ammonium AcetateHCID 108878632,4-PiperidinedioneHCID 89781970HCID 89781970, compound

Product 1

HCID 89783869HCID 89783869, compoundYield 25.4%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-(2-chloro-7-fluoroquinolin-8-yl)ethanone (237 mg, 1.060 mmol) in 3 mL DCM at 0° C. was added Et3N (0.19 mL, 1.38 mmol) followed by TBSOTf (0.27 mL, 1.17 mmol dropwise). The reaction was stirred for 1 h, and was partitioned between saturated NaHCO3 and CH2Cl2. The aq. layer was extracted with CH2Cl2 (3×), and the crude material was concentrated to a yellow oil. The resulting oil was taken up in THF (6 mL), treated with water (0.31 mL, 16.9 mmol) and NBS (198 mg, 1.113 mmol). After 35 min, the mixture was partitioned between water and Et2O. The organic layer was sequentially washed with saturated NaHCO3, water, and saturated and NaCl, and then dried over anhydrous MgSO4, filtered, and concentrated in vacuo to give a yellow, viscous oil. This oil was treated with ammonium acetate (327 mg, 4.24 mmol) and piperidine-2,4-dione (144 mg, 1.272 mmol) and EtOH (6.0 mL) and stirred at RT for 5 min. The resulting yellow slurry was placed in a 50° C. bath for 16 h, cooled, and concentrated in vacuo. The crude residue was purified by silica gel chromatography (0-20% MeOH in DCM), affording 2-(2-chloro-7-fluoroquinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (84.8 mg, 0.269 mmol, 25.3% yield) as a orange solid: 1H NMR (400 MHz, MeOH-d4) δ ppm 8.29 (1H, d, J=8.6 Hz), 8.16 (1H, d, J=7.4 Hz), 7.75 (1H, d, J=11.7 Hz), 7.49 (1H, d, J=8.6 Hz), 7.15 (1H, d, J=3.7 Hz), 3.64 (2H, t, J=7.0 Hz), 3.03 (2H, t, J=7.0 Hz). 19F NMR (377 MHz, MeOH-d4) δ ppm −113.85 (1F, s). m/z (ESI, +ve ion) 316.1 (M+H)+. m/z (ESI, +ve ion) 316.1 (M+H)+.

Workup

  1. customwas partitioned between saturated NaHCO3 and CH2Cl2
  2. extractionThe aq. layer was extracted with CH2Cl2 (3×)
  3. concentrationthe crude material was concentrated to a yellow oil
  4. waitAfter 35 min
  5. customthe mixture was partitioned between water and Et2O
  6. washThe organic layer was sequentially washed with saturated NaHCO3, water
  7. dry with materialsaturated and NaCl, and then dried over anhydrous MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto give a yellow, viscous oil
  11. stirringstirred at RT for 5 min
  12. customwas placed in a 50° C.
  13. customfor 16 h
  14. temperaturecooled
  15. concentrationconcentrated in vacuo
  16. customThe crude residue was purified by silica gel chromatography (0-20% MeOH in DCM)

Sources & evidence

ORD record
ord-96a892aba67746d3aa8ee781520bd3e4
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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