4-Toluenesulfonyl chloride → 6-Bromo-2-(5-(1,1,1-trifluoro-2-(triisopropylsilyloxy)propan-2-yl)-1,3,4-oxadiazol-2-yl)-5-(trifluoromethyl)pyridin-3-amine

HRID 574210Notes

Reaction equation

HRID 574210 reaction equation
[NH2:1][C:2]1[C:3]([C:13]([NH:15][NH:16][C:17](=O)[C:18]([CH3:34])([O:23][Si:24]([CH:31]([CH3:33])[CH3:32])([CH:28]([CH3:30])[CH3:29])[CH:25]([CH3:27])[CH3:26])[C:19]([F:22])([F:21])[F:20])=[O:14])=[N:4][C:5]([Br:12])=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.S(Cl)(C1C=CC(C)=CC=1)(=O)=O>C(Cl)Cl>[Br:12][C:5]1[N:4]=[C:3]([C:13]2[O:14][C:17]([C:18]([O:23][Si:24]([CH:25]([CH3:26])[CH3:27])([CH:28]([CH3:29])[CH3:30])[CH:31]([CH3:33])[CH3:32])([CH3:34])[C:19]([F:21])([F:22])[F:20])=[N:16][N:15]=2)[C:2]([NH2:1])=[CH:7][C:6]=1[C:8]([F:9])([F:10])[F:11]

Participants

4

Reactant 2

HCID 73974-Toluenesulfonyl chlorideHCID 867295973-Amino-6-bromo-N'-(3,3,3-trifluoro-2-methyl-2-(triisopropylsilyloxy)propanoyl)-5-(trifluoromethyl)picolinohydrazide

Product 1

HCID 867295986-Bromo-2-(5-(1,1,1-trifluoro-2-(triisopropylsilyloxy)propan-2-yl)-1,3,4-oxadiazol-2-yl)-5-(trifluoromethyl)pyridin-3-amine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a cooled (0° C.) solution of 3-amino-6-bromo-N′-(3,3,3-trifluoro-2-methyl-2-(triisopropylsilyloxy) propanoyl)-5-(trifluoromethyl)picolinohydrazide (5.42 g, 9.10 mmol) in DCM (50 ml) was added TEA (3.81 ml, 27.3 mmol). The resulting solution was stirred at 0° C. for 5 minutes and treated with Tosyl chloride (5.21 g, 27.3 mmol). The mixture was allowed to warm to RT and stirred for 48 h. The reaction mixture was partitioned between DCM (100 ml) and water (100 ml), phases shaken and separated. The organic portion was washed with 1M NaOH (100 ml), 1M HCl (100 ml), water (100 ml), brine (100 ml), dried (MgSO4) (˜10 g) and concentrated in vacuo to give an orange oil. Purification of the oil by chromatography on silica eluting with 0-15% EtOAc in iso-hexane afforded the title compound; LC-MS Rt=7.41 min [M+H]+ 577/579 Method 10minLC_v003.

Workup

  1. temperatureto warm to RT
  2. stirringstirred for 48 h
  3. customThe reaction mixture was partitioned between DCM (100 ml) and water (100 ml), phases
  4. stirringshaken
  5. customseparated
  6. washThe organic portion was washed with 1M NaOH (100 ml), 1M HCl (100 ml), water (100 ml), brine (100 ml)
  7. dry with materialdried (MgSO4) (˜10 g)
  8. concentrationconcentrated in vacuo
  9. customto give an orange oil
  10. customPurification of the oil by chromatography on silica eluting with 0-15% EtOAc in iso-hexane

Sources & evidence

ORD record
ord-e7ec9d0b9bcd48629a812171d23f356a
Source dataset
uspto-grants-2015_05
Patent number
US09034879B2

Reaction notes

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