1-Hydroxybenzotriazole → 5-(4-(3-Bromobenzyl)-5-methylthiazol-2-yl)-3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazole

HRID 517554

Reaction equation

HRID 517554 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][CH:19]=1)[CH2:5][C:6]1[N:7]=[C:8]([C:12]([O:14]CC)=O)[S:9][C:10]=1[CH3:11].CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.O[NH:43][C:44](=[NH:56])[C:45]1[CH:50]=[CH:49][C:48]([O:51][C:52]([F:55])([F:54])[F:53])=[CH:47][CH:46]=1>CN(C=O)C.CC(O)=O.O.CCOC(C)=O>[Br:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][CH:19]=1)[CH2:5][C:6]1[N:7]=[C:8]([C:12]2[O:14][N:56]=[C:44]([C:45]3[CH:46]=[CH:47][C:48]([O:51][C:52]([F:53])([F:54])[F:55])=[CH:49][CH:50]=3)[N:43]=2)[S:9][C:10]=1[CH3:11]

Participants

9

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27333094-(Trifluoromethoxy)benzamidoximeHCID 86711493Ethyl 4-(3-bromobenzyl)-5-methylthiazole-2-carboxylate

Product 1

HCID 867114955-(4-(3-Bromobenzyl)-5-methylthiazol-2-yl)-3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazoleYield 68%

Reagents, catalysts & solvents 4

HCID 176Acetic AcidCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of ethyl 4-(3-bromobenzyl)-5-methylthiazole-2-carboxylate (0.06 mmol, crude from previous step), EDC.HCl (12 mg, 0.1 mmol) and HOBT (10 mg, 0.1 mmol) in DMF (0.4 mL) was stirred at RT for 30 min. N-hydroxy-4-(trifluoromethoxy)benzimidamide (15 mg, 0.07 mmol) was added and the reaction mixture was stirred for 1 h at RT. DMF (2 mL) was added to the mixture with 2 drops of AcOH. The mixture was subsequently heated to 140° C. for additional 2 h and then cooled to RT, diluted with H2O and taken into EtOAc. The organic layer was washed with NaHCO3, concentrated, and purified by silica gel column chromatography(0-45% EtOAc/Hexane) to give the titled compound (19 mg, 68%). MS (ES+) C20H13BrF3N3O2S requires: 495, 497, found: 496, 498 [M+H]+(1:1).

Workup

  1. temperatureThe mixture was subsequently heated to 140° C. for additional 2 h
  2. temperaturecooled to RT
  3. washThe organic layer was washed with NaHCO3
  4. concentrationconcentrated
  5. custompurified by silica gel column chromatography(0-45% EtOAc/Hexane)

Sources & evidence

ORD record
ord-a2786c6924934814a4cea2356ca0a92b
Source dataset
uspto-grants-2015_08
Patent number
US09115120B2

Linked notes

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