Sodium Carbonate → 7-(4-Cyclopropyl-5-fluoropyridin-3-yl)-9-fluoro-1-methyl-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinoline

HRID 921972노트

반응식

HRID 921972 반응식
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([F:11])[C:7]=1[CH:8]1[CH2:10][CH2:9]1.C(=O)([O-])[O-].[Na+].[Na+].[F:18][C:19]1[CH:20]=[C:21](B(O)O)[CH:22]=[C:23]2[C:28]=1[N:27]1[C:29]([CH3:32])=[N:30][N:31]=[C:26]1[CH2:25][CH2:24]2>COCCOC.O>[CH:8]1([C:7]2[C:6]([F:11])=[CH:5][N:4]=[CH:3][C:2]=2[C:21]2[CH:22]=[C:23]3[C:28](=[C:19]([F:18])[CH:20]=2)[N:27]2[C:29]([CH3:32])=[N:30][N:31]=[C:26]2[CH2:25][CH2:24]3)[CH2:10][CH2:9]1

참가 물질

6

반응물 3

HCID 10340Sodium CarbonateHCID 717433633-Bromo-4-cyclopropyl-5-fluoropyridineHCID 89853586(9-Fluoro-1-methyl-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolin-7-yl)boronic acid

생성물 1

HCID 717673277-(4-Cyclopropyl-5-fluoropyridin-3-yl)-9-fluoro-1-methyl-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinoline

시약·촉매·용매 2

HCID 962Water용매HCID 80711,2-Dimethoxyethane용매

실험 절차

3-Bromo-4-cyclopropyl-5-fluoropyridine (462 mg, 2.14 mmol) was dissolved in a mixture of DME (3.55 mL) and water (3.55 mL). Sodium carbonate (226 mg, 2.14 mmol), (9-fluoro-1-methyl-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolin-7-yl)boronic acid (1-6, 176 mg, 0.71 mmol) and tetrakis triphenylphosphine palladium catalyst (4.11 mg, 3.6 mop were added. The mixture was deoxygenated under reduced pressure, flushed with nitrogen and heated under reflux for 18 h. After cooling to room temperature, ethyl acetate (10 mL) and water (10 mL) were added and the organic layer was separated. The water phase was extracted with ethyl acetate (2×10 mL). The combined organic phases were washed with brine, dried over Na2SO4, filtered over a short plug of Celite® and evaporated under reduced pressure. The crude compound was purified using preparative thin layer chromatography (ethyl acetate/ethanol 6:4) in order to yield the title compound as a white solid; 1H NMR (CD3SOCD3, 500 MHz) δ 8.49 (d, J=2.5 Hz, 1H), 8.35 (s, 1H), 7.60 (dd, J=1.8, 12.0 Hz, 1H), 7.52 (d, J=1.8 Hz, 1H), 3.80 (br. s, 4H), 2.54-2.52 (m, 3H), 1.96-1.95 (m, 1H), 0.89-0.87 (m, 2H), 0.68-0.67 (m, 2H); MS (ESI): m/z=338.97 [M+H]+.

후처리

  1. customThe mixture was deoxygenated under reduced pressure
  2. customflushed with nitrogen
  3. temperatureheated
  4. temperatureunder reflux for 18 h
  5. additionethyl acetate (10 mL) and water (10 mL) were added
  6. customthe organic layer was separated
  7. extractionThe water phase was extracted with ethyl acetate (2×10 mL)
  8. washThe combined organic phases were washed with brine
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered over a short plug of Celite®
  11. customevaporated under reduced pressure
  12. customThe crude compound was purified

출처 및 근거

ORD 기록
ord-7ede33137a2a471990fd907b9003cc96
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09278093B2

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