3-Vinylpyridine → 9-methyl-6-(2-pyridin-3-yl-ethyl)-2,3,4,5,6,10c-hexahydro-1H-3a,6,7-triaza-cyclopenta[c]fluorene

HRID 1630517Notes

Reaction equation

HRID 1630517 reaction equation
[CH3:1][C:2]1[CH:14]=[N:13][C:12]2[NH:11][C:10]3[CH2:9][CH2:8][N:7]4[CH2:15][CH2:16][CH2:17][CH:6]4[C:5]=3[C:4]=2[CH:3]=1.[CH:18]([C:20]1[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=1)=[CH2:19].[OH-].[Na+]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.O>[CH3:1][C:2]1[CH:14]=[N:13][C:12]2[N:11]([CH2:19][CH2:18][C:20]3[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=3)[C:10]3[CH2:9][CH2:8][N:7]4[CH2:15][CH2:16][CH2:17][CH:6]4[C:5]=3[C:4]=2[CH:3]=1

Participants

6

Reactant 3

HCID 142723-VinylpyridineHCID 14798Sodium HydroxideHCID 67434681HCID 67434681, compound

Product 1

HCID 710076009-methyl-6-(2-pyridin-3-yl-ethyl)-2,3,4,5,6,10c-hexahydro-1H-3a,6,7-triaza-cyclopenta[c]fluoreneYield 39.7%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 9-methyl-2,3,4,5,6,10c-hexahydro-1H-3a,6,7-triaza-cyclopenta[c]fluorene (100 mg, 0.44 mmol), 3-vinyl-pyridine (185 mg, 1.762 mmol), tetrabutylammonium bromide (425 mg, 1.32 mmol) and 50% NaOH solution (6 mL) was stirred at 100° C. for 18 h. The progress of reaction was monitored by TLC and LCMS. The reaction mixture was diluted with water (20 mL) and extracted with EtOAc (2×50 mL). The combined organic layer was washed with brine solution (50 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to yield 9-methyl-6-(2-pyridin-3-yl-ethyl)-2,3,4,5,6,10c-hexahydro-1H-3a,6,7-triaza-cyclopenta[c]fluorene (58 mg). 1H NMR (CDCl3, freebase) δ (ppm): 8.41 (d, 1H), 8.27 (s, 1H), 8.07 (s, 1H), 7.58 (s, 1H), 7.2 (d, 1H), 7.1 (dd, 1H), 4.4 (m, 2 H), 3.99 (bs, 1H), 3.2 (dd, 1H), 3.17 (t, 2H), 2.84-2.7 (m, 3H), 2.5 (m, 1H), 2.41 (s, 3H), 2.2 (dd, 1H), 1.9 (m, 4H). Separation by chiral HPLC provided enantiomers 134a and 134b.

Workup

  1. customThe progress of reaction
  2. extractionextracted with EtOAc (2×50 mL)
  3. washThe combined organic layer was washed with brine solution (50 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-c5c77d6d6d0a41479b1d820ea64fb2ca
Source dataset
uspto-grants-2014_07
Patent number
US08791132B2

Reaction notes

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