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

HRID 381900Notes

Reaction equation

HRID 381900 reaction equation
[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

Participants

7

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
40 °C

Procedure

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.0.5 H2O: C, 53.45; H, 3.81; N, 6.23. Found C, 53.45; H, 3.81; N, 6.23.

Workup

  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

Sources & evidence

ORD record
ord-9ee3e2af55344a9588ab09fe60683f56
Source dataset
uspto-grants-2001_10
Patent number
US06307047B1

Reaction notes

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