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

HRID 46253

반응식

HRID 46253 반응식
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]

참가 물질

10

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 887Methanol용매4회HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매3회

실험 절차

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%.

후처리

  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

출처 및 근거

ORD 기록
ord-8daee7a4864144e99b62da57688e9470
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08541588B2

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