Acetonitrile → HCID 90406458, compound

HRID 1772431Notes

Reaction equation

HRID 1772431 reaction equation
[F:1][C:2]([F:30])([F:29])[O:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH:14]=[N:13][C:12]([C:15]3[CH:20]=[CH:19][C:18](/[C:21](/[CH3:28])=C/C(N=[N+]=[N-])=O)=[CH:17][CH:16]=3)=[N:11]2)=[CH:6][CH:5]=1.[CH:31]([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=1[NH:40][C:41]([NH2:43])=[S:42])([CH3:33])[CH3:32].[C:44](=[O:47])([O-])[O-].[Cs+].[Cs+].[C:50]([O-:53])(=O)[CH3:51].[Na+].BrCC(OC)=O.[C:61](#[N:63])C>C(OCC)(=O)C.C(O)C>[CH:31]([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=1[N:40]1[C:50](=[O:53])[CH2:51][S:42]/[C:41]/1=[N:43]\[C:44]([NH:63]/[CH:61]=[C:21](/[C:18]1[CH:19]=[CH:20][C:15]([C:12]2[N:13]=[CH:14][N:10]([C:7]3[CH:8]=[CH:9][C:4]([O:3][C:2]([F:1])([F:30])[F:29])=[CH:5][CH:6]=3)[N:11]=2)=[CH:16][CH:17]=1)\[CH3:28])=[O:47])([CH3:33])[CH3:32]

Participants

9

Reactant 6

HCID 6342AcetonitrileHCID 10796Cesium carbonateHCID 60984Methyl bromoacetateHCID 517045Sodium AcetateHCID 2759507(2-(Propan-2-yl)phenyl)thioureaHCID 90404286(E)-3-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)but-2-enoyl azide

Product 1

HCID 90406458HCID 90406458, compoundYield 37%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

(E)-3-(4-(1-(4-(Trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)but-2-enoyl azide (C29) (0.28 g, 0.68 mmol) in acetonitrile (3.4 mL) was heated at 80° C. for 3 hours. The reaction was cooled and 1-(2-isopropylphenyl)thiourea (0.14 g, 0.74 mmol) and cesium carbonate (0.28 g, 0.86 mmol) were added. The reaction was stirred at room temperature overnight, diluted with ethyl acetate and washed with water. The organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated to provide an orange foam. To the crude material (0.39 g) was added sodium acetate (0.082 g, 1.0 mmol), ethanol (3.4 mL), and methyl 2-bromoacetate (0.10 mL, 1.0 mmol). The reaction mixture was heated at 65° C. for 3 hours. The reaction was cooled, diluted with ethyl acetate, and washed with water. The organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated. The crude compound was loaded onto a Celite® cartridge with dichloromethane and purified by flash column chromatography using 0-100% ethyl acetate/B, where B=1:1 dichloromethane/hexanes, as eluent to afford the title compound as an orange sticky gum (0.16 g, 37%).

Workup

  1. temperatureThe reaction was cooled
  2. washwashed with water
  3. dry with materialThe organic layers were dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto provide an orange foam
  7. temperatureThe reaction mixture was heated at 65° C. for 3 hours
  8. temperatureThe reaction was cooled
  9. washwashed with water
  10. dry with materialThe organic layers were dried over anhydrous sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. custompurified by flash column chromatography

Sources & evidence

ORD record
ord-6eaeeab3eba740ca99f3070734ec16c6
Source dataset
uspto-grants-2016_02
Patent number
US09249133B2

Reaction notes

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