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

HRID 517548

Reaction equation

HRID 517548 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:15]=[CH:16][CH:17]=1)[CH2:5][C:6]1[N:7]=[C:8]([C:12]([OH:14])=O)[O:9][C:10]=1[CH3:11].CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.O[NH:41][C:42](=[NH:54])[C:43]1[CH:48]=[CH:47][C:46]([O:49][C:50]([F:53])([F:52])[F:51])=[CH:45][CH:44]=1>CN(C=O)C.O>[Br:1][C:2]1[CH:3]=[C:4]([CH:15]=[CH:16][CH:17]=1)[CH2:5][C:6]1[N:7]=[C:8]([C:12]2[O:14][N:54]=[C:42]([C:43]3[CH:44]=[CH:45][C:46]([O:49][C:50]([F:51])([F:52])[F:53])=[CH:47][CH:48]=3)[N:41]=2)[O:9][C:10]=1[CH3:11]

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27333094-(Trifluoromethoxy)benzamidoximeHCID 86711488HCID 86711488, compound

Product 1

HCID 733306455-(4-(3-Bromobenzyl)-5-methyloxazol-2-yl)-3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazoleYield 7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

A solution of 4-(3-bromobenzyl)-5-methyloxazole-2-carboxylic acid (300 mg, 1.0 mmol), EDC.HCl (191 mg, 1.0 mmol) and HOBT (135 mg, 1.0 mmol) in DMF (10 mL) was stirred at RT for 2 h, and then N-hydroxy-4-(trifluoromethoxy)benzimidamide (220 mg, 1.0 mmol) was added. The mixture was stirred at 70° C. overnight, cooled to RT, treated with H2O (50 mL) and extracted with EtOAc (3×20 mL). The combined organic layers were washed with H2O (10 mL) and brine (10 mL), dried over Na2SO4, filtered, concentrated and purified by silica gel column chromatography (EtOAc:Petroleum ether=1:5) to afford 5-(4-(3-bromobenzyl)-5-methyloxazol-2-yl)-3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazole as a yellow oil (19 mg, 7%). MS (ES+) C20H13BrF3N3O3 requires 479, 481, found: 480, 482 [M+2+H]+(1:1). 1H NMR (500 MHz, CDCl3) δ 8.24 (d, J=8.5 Hz, 2H), 7.41-7.34 (m, 4H), 7.22-7.19 (m, 2H), 3.94 (s, 2H), 2.44 (s, 3H).

Workup

  1. temperaturecooled to RT
  2. extractionextracted with EtOAc (3×20 mL)
  3. washThe combined organic layers were washed with H2O (10 mL) and brine (10 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified by silica gel column chromatography (EtOAc:Petroleum ether=1:5)

Sources & evidence

ORD record
ord-cb2e11673c2e4e888104ea001e13b2d9
Source dataset
uspto-grants-2015_08
Patent number
US09115120B2

Linked notes

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