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

HRID 1241780Notes

Reaction equation

HRID 1241780 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-bad1d7688afd44dcaff418683604c1d2
Source dataset
uspto-grants-2006_10
Patent number
US07115591B2

Reaction notes

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