Ammonia → 2,5-difluoro-4-[2-pyridazin-4-yl-4-(trifluoromethyl)phenoxy]-N-1,2,4-thiadiazol-5-ylbenzenesulfonamide

HRID 1692216Notes

Reaction equation

HRID 1692216 reaction equation
COC1C=C(OC)C=CC=1C[N:6]([C:19]1[S:23][N:22]=[CH:21][N:20]=1)[S:7]([C:10]1[CH:15]=[C:14]([F:16])[C:13](F)=[CH:12][C:11]=1[F:18])(=[O:9])=[O:8].[N:30]1[CH:35]=[CH:34][C:33]([C:36]2[CH:41]=[C:40]([C:42]([F:45])([F:44])[F:43])[CH:39]=[CH:38][C:37]=2[OH:46])=[CH:32][N:31]=1.C(=O)([O-])[O-].[K+].[K+].Cl.FC(F)(F)C(O)=O.N>CN(C)C=O.ClCCl.CO>[F:18][C:11]1[CH:12]=[C:13]([O:46][C:37]2[CH:38]=[CH:39][C:40]([C:42]([F:43])([F:44])[F:45])=[CH:41][C:36]=2[C:33]2[CH:34]=[CH:35][N:30]=[N:31][CH:32]=2)[C:14]([F:16])=[CH:15][C:10]=1[S:7]([NH:6][C:19]1[S:23][N:22]=[CH:21][N:20]=1)(=[O:8])=[O:9]

Participants

10

Reactant 6

HCID 222AmmoniaHCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 59436583N-(2,4-Dimethoxybenzyl)-2,4,5-trifluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamideHCID 1357416972-(Pyridazin-4-yl)-4-(trifluoromethyl)phenol

Product 1

HCID 468413512,5-difluoro-4-[2-pyridazin-4-yl-4-(trifluoromethyl)phenoxy]-N-1,2,4-thiadiazol-5-ylbenzenesulfonamide

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent4×HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent3×

Procedure

The mixture of N-(2,4-dimethoxybenzyl)-2,4,5-trifluoro-N-1,2,4-thiadiazol-5-ylbenzenesulfonamide (Preparation 647, 44 mg, 0.10 mmol), 2-pyridazin-4-yl-4-(trifluoromethyl)phenol (Preparation 712, 34 mg, 0.10 mmol), and potassium carbonate (55 mg, 0.40 mmol) in N,N-dimethylformamide (1.0 ml) was stirred at room temperature for 24 hours. The reaction mixture was poured into aqueous 2 M hydrochloric acid solution (5.0 ml) and filtered to give a solid. The solid was dissolved in dichloromethane (1.0 ml) and trifluoroacetic acid (1.0 ml) was added to the solution. The resulting solution was stirred for 16 hours. Methanol (5.0 ml) was added to the reaction mixture and filtered off polymeric solid. The filtrate was concentrated in vacuo to give a residue. The residue was passed through a 5 g SCX™ column with 1:1 dichloromethane:methanol solution and then 1:0.75:0.25 dichloromethane:methanol:7N ammonia solution in methanol. The filtrate was concentrated in vacuo and purified by HPLC. Yield 7.3 mg, 14%.

Workup

  1. filtrationfiltered
  2. customto give a solid
  3. stirringThe resulting solution was stirred for 16 hours
  4. filtrationfiltered off polymeric solid
  5. concentrationThe filtrate was concentrated in vacuo
  6. customto give a residue
  7. concentrationThe filtrate was concentrated in vacuo
  8. custompurified by HPLC

Sources & evidence

ORD record
ord-e78a27e210c24548a8e85b9ef76c3100
Source dataset
uspto-grants-2012_04
Patent number
US08153814B2

Reaction notes

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