4-Toluenesulfonyl chloride → 3-(5-Benzyl-1,3,4-oxadiazol-2-yl)-5-bromo-6-(trifluoromethyl)pyrazin-2-amine

HRID 574203Notes

Reaction equation

HRID 574203 reaction equation
[NH2:1][C:2]1[C:3]([C:13]([NH:15][NH:16][C:17](=[O:25])[CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=O)=[N:4][C:5]([Br:12])=[C:6]([C:8]([F:11])([F:10])[F:9])[N:7]=1.S(Cl)(C1C=CC(C)=CC=1)(=O)=O.CCN(P1(N(C)CCCN1C)=NC(C)(C)C)CC>C1COCC1>[CH2:18]([C:17]1[O:25][C:13]([C:3]2[C:2]([NH2:1])=[N:7][C:6]([C:8]([F:9])([F:11])[F:10])=[C:5]([Br:12])[N:4]=2)=[N:15][N:16]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

5

Reactant 3

HCID 73974-Toluenesulfonyl chlorideHCID 35138512-((1,1-Dimethylethyl)imino)-N,N-diethylhexahydro-1,3-dimethyl-2lambda5-1,3,2-diazaphosphorin-2-amineHCID 867295913-Amino-6-bromo-N'-(2-phenylacetyl)-5-(trifluoromethyl)pyrazine-2-carbohydrazide

Product 1

HCID 715156353-(5-Benzyl-1,3,4-oxadiazol-2-yl)-5-bromo-6-(trifluoromethyl)pyrazin-2-amine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 3-amino-6-bromo-N′-(2-phenylacetyl)-5-(trifluoromethyl)pyrazine-2-carbohydrazide (step 1) (92 mg, 0.220 mmol) in THF (2 ml) was added a solution of TsCl (50 mg, 1.200 mmol) in THF (0.5 ml). The resulting solution was then added to PS-BEMP (384 mg, 1.100 mmol) and the mixture was heated using microwave radiation at 120° C. for 10 min. The reaction mixture was loaded onto an Isolute® PE-AX/SCX-2 cartridge (10 g, Solid Phase Extraction) pre-wetted with THF. The cartridge was eluted with THF (40 ml) and the organic portion was concentrated in vacuo. The crude product was purified by chromatography on silica eluting with 20% EtOAc/iso-hexane followed by further purification by preparative HPLC to afford the title compound; 1H NMR (400 MHz, DMSO-d6) δ 7.35 (5H), 4.49 (2H, s). LC-MS Rt=5.76 min [M+H]+ 400.1 Method 10minLC_v002.

Workup

  1. temperaturethe mixture was heated
  2. customat 120° C.
  3. customfor 10 min
  4. extractionThe reaction mixture was loaded onto an Isolute® PE-AX/SCX-2 cartridge (10 g, Solid Phase Extraction)
  5. washThe cartridge was eluted with THF (40 ml)
  6. concentrationthe organic portion was concentrated in vacuo
  7. customThe crude product was purified by chromatography on silica eluting with 20% EtOAc/iso-hexane
  8. customfollowed by further purification by preparative HPLC

Sources & evidence

ORD record
ord-43078a6ad01d4f6ebe00d62b509c5507
Source dataset
uspto-grants-2015_05
Patent number
US09034879B2

Reaction notes

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