Sodium Carbonate → 1-methyl-3-(4-oxopiperidin-1-yl)-4-(4-(quinolin-2-ylmethoxy)phenyl)-1H-pyrrole-2,5-dione

HRID 655414Notes

Reaction equation

HRID 655414 reaction equation
Br[C:2]1[C:3](=[O:16])[N:4]([CH3:15])[C:5](=[O:14])[C:6]=1[N:7]1[CH2:12][CH2:11][C:10](=[O:13])[CH2:9][CH2:8]1.CC1(C)C(C)(C)OB([C:25]2[CH:42]=[CH:41][C:28]([O:29][CH2:30][C:31]3[CH:40]=[CH:39][C:38]4[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=4)[N:32]=3)=[CH:27][CH:26]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:15][N:4]1[C:3](=[O:16])[C:2]([C:25]2[CH:26]=[CH:27][C:28]([O:29][CH2:30][C:31]3[CH:40]=[CH:39][C:38]4[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=4)[N:32]=3)=[CH:41][CH:42]=2)=[C:6]([N:7]2[CH2:12][CH2:11][C:10](=[O:13])[CH2:9][CH2:8]2)[C:5]1=[O:14]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 583680032-((4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)methyl)quinolineHCID 593547873-bromo-1-methyl-4-(4-oxopiperidin-1-yl)-1H-pyrrole-2,5-dione

Product 1

HCID 593548451-methyl-3-(4-oxopiperidin-1-yl)-4-(4-(quinolin-2-ylmethoxy)phenyl)-1H-pyrrole-2,5-dioneYield 53.3%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

To a room temperature, stirred solution of 3-bromo-1-methyl-4-(4-oxopiperidin-1-yl)-1H-pyrrole-2,5-dione (100 mg, 0.34 mmol) in 1,4-dioxane (10 mL) was added 2-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)methyl)quinoline (151 mg, 0.41 mol) under a N2 atmosphere. The reaction mixture was stirred for 30 minutes and then Na2CO3 (87 mg, 1.04 mmol), water (4 mL) and Pd(PPh3)4 (40 mg, 0.03 mmol) were added also under a N2 atmosphere. The resulting mixture was then refluxed for 16 h, diluted with water and extracted with EtOAc (2×20 mL). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The crude material was purified via silica gel column chromatography eluting with 60% EtOAc in hexanes to afford 1-methyl-3-(4-oxopiperidin-1-yl)-4-(4-(quinolin-2-ylmethoxy)phenyl)-1H-pyrrole-2,5-dione (80 mg, 52%) as a solid. 1H NMR (500 MHz, d6-DMSO): δ 8.45 (d, J=7.4 Hz, 1H), 8.12 (t, J=7.2 Hz, 2H) 7.79 (t, J=7.2 Hz, 1H), 7.72 (d, J=7.8 Hz, 1H), 7.64 (t, J=7.6 Hz, 1H), 7.18 (d, J=7.2 Hz, 2H), 7.12 (d, J=7.2 Hz, 2H), 5.38 (s, 2H), 3.62-3.58 (m, 4H), 2.96-2.85 (m, 4H), 2.56 (s, 4H). MS: M′: m/z=441.6; M+H: m/z=442.7. HPLC: 97%, (Condition-B).

Workup

  1. temperatureThe resulting mixture was then refluxed for 16 h
  2. extractionextracted with EtOAc (2×20 mL)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude material was purified via silica gel column chromatography
  8. washeluting with 60% EtOAc in hexanes

Sources & evidence

ORD record
ord-307a4c7de0574f26a5bc2c30c65a7ebe
Source dataset
uspto-grants-2011_12
Patent number
US08071595B2

Reaction notes

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