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 2408621노트

반응식

HRID 2408621 반응식
[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

참가 물질

6

반응물 3

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

생성물 1

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

시약·촉매·용매 2

HCID 74236Tetrabutylammonium Bromide촉매HCID 962Water용매

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온도
100 °C

실험 절차

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, 2H), 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.

후처리

  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

출처 및 근거

ORD 기록
ord-ea8f562d71aa4f77924c934c2f7f5700
출처 데이터셋
uspto-grants-2014_08
특허 번호
US08815843B2

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