3(2H)-Pyridazinone → 2-(2,2,2-Trifluoroethyl)-4-(4-fluorobenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone

HRID 891319노트

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HRID 891319 반응식
[Mg].[F:2][CH:3](Br)[C:4]1C=CC=C[CH:5]=1.[F:11][C:12]([F:33])([F:32])[CH2:13][N:14]1[C:19](=[O:20])[C:18](Cl)=[C:17]([C:22]2[CH:27]=[CH:26][C:25]([S:28]([CH3:31])(=[O:30])=[O:29])=[CH:24][CH:23]=2)[CH:16]=[N:15]1.N1N[C:36](=O)[CH:37]=[CH:38][CH:39]=1>C1COCC1.CCOCC>[F:11][C:12]([F:33])([F:32])[CH2:13][N:14]1[C:19](=[O:20])[C:18]([CH2:36][C:37]2[CH:5]=[CH:4][C:3]([F:2])=[CH:39][CH:38]=2)=[C:17]([C:22]2[CH:27]=[CH:26][C:25]([S:28]([CH3:31])(=[O:30])=[O:29])=[CH:24][CH:23]=2)[CH:16]=[N:15]1

참가 물질

7

반응물 4

HCID 681533(2H)-PyridazinoneHCID 316418[Bromo(fluoro)methyl]benzeneHCID 5462224MagnesiumHCID 219343142-(2,2,2-trifluoroethyl)-4-chloro-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone

생성물 1

HCID 219343022-(2,2,2-Trifluoroethyl)-4-(4-fluorobenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone수율 28%

시약·촉매·용매 2

HCID 3283Diethyl Ether용매HCID 8028Tetrahydrofuran용매

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온도
40 °C

실험 절차

Magnesium turnings (500 mg) were placed in a dry 250 mL round bottom flask. Anhydrous ether (20 mL) was added under N2 at room temperature then fluorobenzyl bromide (3 mL) was added and stirred. The reaction was heated at 40° C. for 2 hours. All magnesium was consumed resulting in a pale brownish-yellow solution. The 2-(2,2,2-trifluoroethyl)-4-chloro-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone prepared in Example 193E was dissolved in dry THF (25 mL) and transferred to the Grignard solution. The mixture was heated for 3 hours. TLC (2:1 hexanes/ethyl acetate) indicated that the pyridazinone starting material was consumed.) The reaction was cooled to room temperature then quenched with a saturated NH4Cl solution. The product was extracted with ethyl acetate (250 mL); and the organic layer was washed with saturated NH4Cl, and brine. The ethyl acetate solution was dried over MgSO4 and filtered. The filtrate was concentrated under reduced pressure. The product was isolated as an orange residue. Purification using a silica gel column (20:80 ethyl acetate/pentanes) provided the title compound as a pale yellow powder (yield: 140 mg, 28%). 1H NMR (300 MHz, CDCl3) δ 3.13 (s, 3H), 4.85 (m, 2H), 6.93 (m, 4H), 7.49 (d, J=9 Hz, 2H) 7.72 (s, 1H), 8.08 (d, J=9 Hz, 2H). MS (DCI/NH3) m/z 441 (M+H)+. Anal. calc. for C20H16F4N2O3S.0.5H2O: C, 53.45; H, 3.81; N, 6.23. Found C, 53.45; H, 3.81; N, 6.23.

후처리

  1. customAll magnesium was consumed
  2. customresulting in a pale brownish-yellow solution
  3. temperatureThe mixture was heated for 3 hours
  4. customwas consumed
  5. temperature) The reaction was cooled to room temperature
  6. customthen quenched with a saturated NH4Cl solution
  7. extractionThe product was extracted with ethyl acetate (250 mL)
  8. washand the organic layer was washed with saturated NH4Cl, and brine
  9. dry with materialThe ethyl acetate solution was dried over MgSO4
  10. filtrationfiltered
  11. concentrationThe filtrate was concentrated under reduced pressure
  12. customThe product was isolated as an orange residue
  13. customPurification

출처 및 근거

ORD 기록
ord-58ce437055764874bbeff5570d2b5804
출처 데이터셋
uspto-grants-2006_02
특허 번호
US07001895B2

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