1,1'-Carbonyldiimidazole → 5-n-Butyl-4-[[2'-[N-[(S)-2,2-dimethylcyclopropanecarbonyl]sulfamoyl]biphenyl-4-yl]methyl]-2,4-dihydro-2-[2-(trifluoromethyl)phenyl]-3H-1,2,4-triazol3-one

HRID 36237

반응식

HRID 36237 반응식
[CH3:1][C:2]1([CH3:8])[CH2:4][C@@H:3]1[C:5](O)=[O:6].C(N1C=CN=C1)(N1C=CN=C1)=O.C1CCN2C(=NCCC2)CC1.[CH2:32]([C:36]1[N:37]([CH2:52][C:53]2[CH:58]=[CH:57][C:56]([C:59]3[CH:64]=[CH:63][CH:62]=[CH:61][C:60]=3[S:65](=[O:68])(=[O:67])[NH2:66])=[CH:55][CH:54]=2)[C:38](=[O:51])[N:39]([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][C:42]=2[C:47]([F:50])([F:49])[F:48])[N:40]=1)[CH2:33][CH2:34][CH3:35]>C1COCC1>[CH2:32]([C:36]1[N:37]([CH2:52][C:53]2[CH:58]=[CH:57][C:56]([C:59]3[CH:64]=[CH:63][CH:62]=[CH:61][C:60]=3[S:65](=[O:68])(=[O:67])[NH:66][C:5]([C@H:3]3[CH2:4][C:2]3([CH3:8])[CH3:1])=[O:6])=[CH:55][CH:54]=2)[C:38](=[O:51])[N:39]([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][C:42]=2[C:47]([F:50])([F:49])[F:48])[N:40]=1)[CH2:33][CH2:34][CH3:35]

참가 물질

6

반응물 4

HCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 10192561(1S)-2,2-Dimethylcyclopropane-1-carboxylic acidHCID 103469025-n-Butyl-2,4-dihydro-4-[(2'-sulfamoylbiphenyl-4-yl)methyl]-2-[2-(trifluoromethyl)phenyl]-3H-1,2,4-triazol-3-one

생성물 1

HCID 117645595-n-Butyl-4-[[2'-[N-[(S)-2,2-dimethylcyclopropanecarbonyl]sulfamoyl]biphenyl-4-yl]methyl]-2,4-dihydro-2-[2-(trifluoromethyl)phenyl]-3H-1,2,4-triazol3-one수율 74%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
50 °C

실험 절차

A solution of (S)-2,2-dimethylcyclopropanecarboxylic acid (194 mg, 1.70 mmol), and carbonyldiimidazole (275 mg, 1.70 mmol) in THF was stirred at 50° C. for 3 hrs. To this was added dropwise a solution of DBU (258 mg, 1.7 mmol) and 5-n-butyl-2,4-dihydro-4-[(2'-sulfamoylbiphenyl-4-yl)methyl]-2-[2-(trifluoromethyl)phenyl]-3H-1,2,4-triazol-3-one (300 mg, 0.57 mmol) (from Example 16, Step C) in THF. After stirring at 50° C. overnight, the reaction mixture was quenched by addition of 5% citric acid and extracted with EtOAc. The organic layers were combined and washed with water, 5% NaHCO3, and brine, and dried over anhydrous Na2SO4. The crude material obtained after filtration and evaporation of volatiles was flash chromatographed over 60 mL silica gel (gradient elution using 0.5-5.0% MeOH/CH2Cl2) to afford the title compound in 74% yield (263 mg) as a white solid, homogeneous by TLC in 5% MeOH/CH2Cl2 ; mass spectrum (FAB) m/e 627 (M+1)+, 649 (M+Na)+ ; mp 93°-95° C.

후처리

  1. customthe reaction mixture was quenched by addition of 5% citric acid
  2. extractionextracted with EtOAc
  3. washwashed with water, 5% NaHCO3, and brine
  4. dry with materialdried over anhydrous Na2SO4
  5. customThe crude material obtained
  6. filtrationafter filtration and evaporation of volatiles
  7. customchromatographed over 60 mL silica gel (gradient elution using 0.5-5.0% MeOH/CH2Cl2)

출처 및 근거

ORD 기록
ord-93bbf038b774465ca5883158b6bde6b2
출처 데이터셋
uspto-grants-1995_05
특허 번호
US05411980

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