1-Hydroxybenzotriazole → 5-(4-Hydroxy-phenyl)-isoxazole-3-carboxylic acid {2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-amide

HRID 1177959Notes

Reaction equation

HRID 1177959 reaction equation
CCN(C(C)C)C(C)C.OC(C(F)(F)F)=O.[NH2:17][CH2:18][C:19]([N:21]1[CH2:26][CH2:25][N:24]([C:27](=[O:38])[C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=2[C:34]([F:37])([F:36])[F:35])[CH2:23][CH2:22]1)=[O:20].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[OH:61][C:62]1[CH:67]=[CH:66][C:65]([C:68]2[O:72][N:71]=[C:70]([C:73](O)=[O:74])[CH:69]=2)=[CH:64][CH:63]=1>CN(C=O)C.O>[O:20]=[C:19]([N:21]1[CH2:22][CH2:23][N:24]([C:27](=[O:38])[C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=2[C:34]([F:37])([F:35])[F:36])[CH2:25][CH2:26]1)[CH2:18][NH:17][C:73]([C:70]1[CH:69]=[C:68]([C:65]2[CH:66]=[CH:67][C:62]([OH:61])=[CH:63][CH:64]=2)[O:72][N:71]=1)=[O:74]

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 10909835-(4-Hydroxyphenyl)isoxazole-3-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 866340882-amino-1-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethanone TFA salt

Product 1

HCID 1359597585-(4-Hydroxy-phenyl)-isoxazole-3-carboxylic acid {2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-amideYield 26.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (65 mg, 0.51 mmol) was added to a stirred solution of 2-amino-1-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethanone TFA salt. (87 mg, 0.20 mmol) in DMF (1 mL). HOBT (28 mg, 0.20 mmol) and EDCI.HCl (39 mg, 0.20 mmol) were then added at room temperature. After 2 minutes, 5-(4-hydroxyphenyl)-isoxazole-3-carboxylic acid (35 mg, 0.17 mmol) was added and the resulting mixture was stirred at room temperature for 4 hrs. Cold water (20 mL) was then added and the product was extracted with EtOAc and the organic layer was washed with brine. The organic phase was dried over Na2SO4 and concentrated under reduced pressure to afford 23 mg (26.7% yield) of 5-(4-hydroxy-phenyl)-isoxazole-3-carboxylic acid {2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-amide. LCMS Purity: 93.77%, HPLC Purity: 90.43%, 1H NMR (DMSO-d6): δ 10.1-10.0 (s, 1H), 8.6-8.5 (s, 1H), 8.0-7.6 (m, 5H), 7.5 (bs, 1H), 7.1 (s, 1H), 6.8 (d, 2H), 4.2-4.1 (d, 2H) 3.8-3.7 (m, 2H), 3.6 (m, 2H), 3.4 (m, 2H), 3.2-3.1 (m, 2H).

Workup

  1. extractionthe product was extracted with EtOAc
  2. washthe organic layer was washed with brine
  3. dry with materialThe organic phase was dried over Na2SO4
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-1f95600cdfe7403bb282ccf56e328735
Source dataset
uspto-grants-2010_11
Patent number
US07842696B2

Reaction notes

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