Ammonia → 2-(2,2,2-trifluoroethyl)-4-(4-fluoro-3-methylphenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone

HRID 381911Notes

Reaction equation

HRID 381911 reaction equation
B(O)O.[F:4][C:5]([F:26])([F:25])[CH2:6][N:7]1[C:12](=[O:13])[C:11](Cl)=[C:10]([C:15]2[CH:20]=[CH:19][C:18]([S:21]([CH3:24])(=[O:23])=[O:22])=[CH:17][CH:16]=2)[CH:9]=[N:8]1.[F-:27].[Cs+].N>COCCOC.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O>[F:4][C:5]([F:26])([F:25])[CH2:6][N:7]1[C:12](=[O:13])[C:11]([C:17]2[CH:18]=[CH:19][C:20]([F:27])=[C:15]([CH3:10])[CH:16]=2)=[C:10]([C:15]2[CH:20]=[CH:19][C:18]([S:21]([CH3:24])(=[O:23])=[O:22])=[CH:17][CH:16]=2)[CH:9]=[N:8]1

Participants

8

Reactant 4

HCID 222AmmoniaHCID 25953Cesium fluorideHCID 61668Boronic AcidHCID 219343142-(2,2,2-trifluoroethyl)-4-chloro-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone

Product 1

HCID 219340472-(2,2,2-trifluoroethyl)-4-(4-fluoro-3-methylphenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

The boronic acid (231 mg, 1.5 mmol), prepared in example 210A, 2-(2,2,2-trifluoroethyl)-4-chloro-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone (500 mg, 1.36 mmol), tetrakis-(triphenylphosphine)-palladium(0) (47 mg, 0.041 mmol), and CsF (413 mg, 2.72 mmol) were stirred at reflux in DME (20 mL) under N2 for 5 hours. TLC (1:1 hexanes/ethyl acetate) indicated that all the starting material was consumed. Volatiles were removed in vacuo. The residue was partitioned between water and ethyl acetate. The organic layer was washed with brine, dried over MgSO4, and filtered. The filtrate was concentrated in vacuo. An off white powder was obtained (yield: 275 mg, 46%). mp 88-91° C.; 1H NMR (300 MHz, CDCl3, a mixture of rotamers) δ 2.2, 2.25 (2d, J=1.5 Hz, 3H) 3.05, 3.09 (2 s, 3H) 4.78-4.92 (m, 2H) 6.61-6.8 (m, 1H) 6.82-6.98 (m, 1H) 7.35 (d, J=9 Hz, 1H) 7.78 (d, J=9 Hz, 1H) 7.86-8.09 (m, 4H). 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, 53.17; H, 3.65; N, 5.88.

Workup

  1. customwas consumed
  2. customVolatiles were removed in vacuo
  3. customThe residue was partitioned between water and ethyl acetate
  4. washThe organic layer was washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated in vacuo
  8. customAn off white powder was obtained (yield: 275 mg, 46%)

Sources & evidence

ORD record
ord-33825b0c4bce440b80909e1f077ef988
Source dataset
uspto-grants-2001_10
Patent number
US06307047B1

Reaction notes

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