1-Hydroxybenzotriazole → HCID 57874366, compound

HRID 1093759Notes

Reaction equation

HRID 1093759 reaction equation
CCN(C(C)C)C(C)C.[OH:10][C:11]1[CH:12]=[C:13]([C:17]2[O:21][N:20]=[C:19]([C:22]([OH:24])=O)[CH:18]=2)[CH:14]=[CH:15][CH:16]=1.C(OC1C=CC=CC=1C(=O)C)C1C=CC=CC=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.[NH2:65][CH2:66][C:67]([N:69]1[CH2:74][CH2:73][CH:72]([O:75][C:76]2[CH:81]=[CH:80][CH:79]=[C:78]([C:82]([F:85])([F:84])[F:83])[CH:77]=2)[CH2:71][CH2:70]1)=[O:68]>CN(C=O)C.O>[O:68]=[C:67]([N:69]1[CH2:70][CH2:71][CH:72]([O:75][C:76]2[CH:81]=[CH:80][CH:79]=[C:78]([C:82]([F:85])([F:83])[F:84])[CH:77]=2)[CH2:73][CH2:74]1)[CH2:66][NH:65][C:22]([C:19]1[CH:18]=[C:17]([C:13]2[CH:14]=[CH:15][CH:16]=[C:11]([OH:10])[CH:12]=2)[O:21][N:20]=1)=[O:24]

Participants

9

Reactant 6

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 5205131-[2-(Benzyloxy)phenyl]ethan-1-oneHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 31571005-(3-Hydroxy-phenyl)-isoxazole-3-carboxylic acidHCID 665915472-Amino-1-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethanone hydrochloride

Product 1

HCID 57874366HCID 57874366, compoundYield 37.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (133 mg, 1.03 mmol) was added to a stirred solution of 5-(3-hydroxy-phenyl)-isoxazole-3-carboxylic acid (61 mg, 0.294 mmol)) (prepared by the method used for the synthesis of Intermediate 25, starting from 2′-benzyloxyacetophenone) in DMF (2 mL) followed by HOBt (41.7 mg, 0.308 mmol) and EDCI.HCl (59 mg, 0.308 mmol). After 2 minutes 2-amino-1-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethanone hydrochloride (99 mg, 0.294 mmol) (prepared according to Step 1 and 5 of the General Scheme) was added to the reaction mixture and stirring was continued at ambient temperature overnight. The reaction mixture was diluted with cold water, extracted with ethyl acetate, dried over sodium sulfate and concentrated under reduced pressure The residue was purified by washing with ethylacetate to afford 54 mg (37.7% Yield) of 5-(3-hydroxy-phenyl)-isoxazole-3-carboxylic acid {2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide. LC/MS [M+H]+: 490, 94.4%. 1H NMR (300 MHz, DMSO-d6): δ9.9 (s, 1H), 8.65 (t, 1H), 7.5 (t, 1H), 7.3 (m, 7H), 6.95 (m, 1H), 4.8 (m, 1H), 4.2 (d, 2H), 3.9 (s, 1H), 3.7 (m, 1H), 3.4 (m, 2H), 2.0 (m, 2H), 1.6 (m, 2H).

Workup

  1. customprepared by the method
  2. additionwas added to the reaction mixture
  3. extractionextracted with ethyl acetate
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated under reduced pressure The residue
  6. customwas purified
  7. washby washing with ethylacetate

Sources & evidence

ORD record
ord-c2032c6e7bf44d30934a93c5344f79f7
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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