1-Hydroxybenzotriazole → HCID 25164522, compound

HRID 1177957Notes

Reaction equation

HRID 1177957 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.[CH2:61]([O:68][C:69]1[CH:74]=[CH:73][C:72]([C:75]2[O:79][N:78]=[C:77]([C:80](O)=[O:81])[CH:76]=2)=[CH:71][CH:70]=1)[C:62]1[CH:67]=[CH:66][CH:65]=[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:80]([C:77]1[CH:76]=[C:75]([C:72]2[CH:71]=[CH:70][C:69]([O:68][CH2:61][C:62]3[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=3)=[CH:74][CH:73]=2)[O:79][N:78]=1)=[O:81]

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 54846851HCID 54846851, compoundHCID 866340882-amino-1-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethanone TFA salt

Product 1

HCID 25164522HCID 25164522, compoundYield 48%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (65.5 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 (27 mg, 0.20 mmol) and EDCI.HCl (38 mg, 0.20 mmol) were then added at room temperature. After 2 minutes, 5-(4-benzyloxyphenyl)-isoxazole-3-carboxylic acid (50 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. the resulting residue was purified by column chromatography (using silica gel 60-120 mesh and 2.5% methanol in chloroform as eluent) to afford 48 mg (48% yield) of 5-(4-benzyloxy-phenyl)-isoxazole-3-carboxylic acid {2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-amide. LCMS Purity: 83.69%, HPLC Purity: 99.66%, 1H NMR (DMSO-d6): δ 8.6 (t, 1H), 8.0-7.8 (m, 3H), 7.8-7.7 (d, 1H), 7.7 (d, 1H), 7.6-7.5 (m, 1H), 7.4 (m, 4H), 7.3-7.2 (s, 1H), 7.2 (d, 2H), 5.0 (s, 2H), 4.3-4.2 (dd, 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
  5. customthe resulting residue was purified by column chromatography (using silica gel 60-120 mesh and 2.5% methanol in chloroform as eluent)

Sources & evidence

ORD record
ord-6035aa9336bc4b779c5d6ec6cd352996
Source dataset
uspto-grants-2010_11
Patent number
US07842696B2

Reaction notes

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