Sodium Iodide → HCID 21933970, compound

HRID 891324Notes

Reaction equation

HRID 891324 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:13](=[O:14])[C:12]([CH2:15]Br)=[C:11]([C:17]3[CH:22]=[CH:21][C:20]([S:23]([CH3:26])(=[O:25])=[O:24])=[CH:19][CH:18]=3)[CH:10]=[N:9]2)=[CH:4][CH:3]=1.[Na+].[I-].[CH3:29][C:30]([SH:33])([CH3:32])[CH3:31]>CC(C)=O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:13](=[O:14])[C:12]([CH2:15][S:33][C:30]([CH3:32])([CH3:31])[CH3:29])=[C:11]([C:17]3[CH:22]=[CH:21][C:20]([S:23]([CH3:26])(=[O:25])=[O:24])=[CH:19][CH:18]=3)[CH:10]=[N:9]2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 5238Sodium IodideHCID 6387tert-Butyl mercaptanHCID 21933937HCID 21933937, compound

Product 1

HCID 21933970HCID 21933970, compoundYield 60.2%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent2×

Conditions

Temperature
23 °C

Procedure

A 0° C. solution of the 2-(4-fluorophenyl)-4-bromomethyl-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone prepared in Example 194F (92.5 mg, 0.212 mmol) in acetone (2.5 mL) was treated with NaI (35 mg, 0.233 mmol), and after 5 minutes, the cooling bath was removed and the reaction warmed to 23° C. After 30 minutes, conversion to the 2-(4-fluorophenyl)-4-iodomethyl-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone was complete (thin layer chromatography, ethyl acetate/hexanes 4:1). The NaBr and residual NaI were filtered off through a pad of Celite®. Additional acetone (2 mL) was added along with 2-methyl-2-propanethiol (20.5 mg, 0.227 mmol), and the solution cooled to 0° C. before addition of Ag2CO3 (63 mg, 0.227 mmol). After 5 minutes, the cooling bath was removed and the solution warmed to 23° C. for 5 hours. The reaction mixture was filtered through Celite® and concentrated in vacuo. The residue was chromatographed (flash silica gel, ethyl acetate/hexanes gradient 1:1 to 3:2) to provide the product (yield: 57 mg, 60%). mp 50-70° C. 1H NMR (300 MHz, CDCl3) δ 1.34 (s, 9H), 3.14 (s, 3H), 3.65 (s, 2H), 7.13-7.21 (m, 2H), 7.63-7.70 (m, 2H), 7.79 (s, 1H), 7.84 (d, J=8.7 Hz, 2H), 8.13 (d, J=8.7 Hz, 2H). MS (APCI+) m/z 447 (M+H)+. Anal. calc. for C22H23FN2O3S2: C, 59.17; H, 5.19; N, 6.27. Found: C, 59.48; H, 5.36; N, 5.90.

Workup

  1. customthe cooling bath was removed
  2. waitAfter 30 minutes
  3. filtrationThe NaBr and residual NaI were filtered off through a pad of Celite®
  4. waitAfter 5 minutes
  5. customthe cooling bath was removed
  6. temperaturethe solution warmed to 23° C. for 5 hours
  7. filtrationThe reaction mixture was filtered through Celite®
  8. concentrationconcentrated in vacuo
  9. customThe residue was chromatographed (flash silica gel, ethyl acetate/hexanes gradient 1:1 to 3:2)

Sources & evidence

ORD record
ord-3dbdad0dda9443e2a246e04ba26022fa
Source dataset
uspto-grants-2006_02
Patent number
US07001895B2

Reaction notes

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