1-Hydroxybenzotriazole → HCID 57874482, compound

HRID 1093756Notes

Reaction equation

HRID 1093756 reaction equation
CCN(C(C)C)C(C)C.[C:10]1([C:16]2[O:20][N:19]=[C:18]([C:21]([NH:23][CH2:24][C:25]([OH:27])=O)=[O:22])[CH:17]=2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.[F:51][C:52]([F:67])([F:66])[C:53]1[CH:54]=[C:55]([CH:63]=[CH:64][CH:65]=1)[O:56][CH:57]1[CH2:62][CH2:61][NH:60][CH2:59][CH2:58]1>CN(C=O)C.O>[O:27]=[C:25]([N:60]1[CH2:59][CH2:58][CH:57]([O:56][C:55]2[CH:63]=[CH:64][CH:65]=[C:53]([C:52]([F:51])([F:66])[F:67])[CH:54]=2)[CH2:62][CH2:61]1)[CH2:24][NH:23][C:21]([C:18]1[CH:17]=[C:16]([C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)[O:20][N:19]=1)=[O:22]

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 433543392-[(5-Phenyl-1,2-oxazol-3-yl)formamido]acetic acidHCID 467356844-[3-(Trifluoromethyl)phenoxy]piperidine--hydrogen chloride (1/1)

Product 1

HCID 57874482HCID 57874482, compoundYield 51.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (96 mg, 0.745 mmol) was added to a stirred solution of [(5-phenyl-isoxazole-3-carbonyl)-amino]-acetic acid (67 mg, 0.27 mmol) in DMF (3 mL) followed by HOBt (36 mg, 0.273 mmol) and EDCI.HCl (62 mg, 0.32 mmol). After 2 minutes 4-(3-trifluoromethyl-phenoxy)-piperidine hydrochloride (70 mg, 0.248 mmol) (prepared by method used for the synthesis of Intermediate 15) 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 column chromatography (using 60-120 silica gel and 50% EtOAc in hexane as eluent) to afford 60 mg (34% Yield) of 5-phenyl-isoxazole-3-carboxylic acid {2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide. LC/MS [M+H]+: 474, 70.17%. 1H NMR (300 MHz, DMSO-d6): δ8.7-8.6 (t, 1H), 8.0-7.9 (m, 2H), 7.6-7.5 (m, 4H), 7.4 (s, 1H), 7.3-7.26 (t, 3H), 4.8 (m, 1H), 4.2 (d, 2H), 3.9 (m, 1H), 3.7 (m, 1H), 3.5 (m, 1H), 3.3 (m, 1H), 2.0 (m, 2H), 1.8-1.4 (m, 2H).

Workup

  1. additionwas added to the reaction mixture
  2. extractionextracted with ethyl acetate
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated under reduced pressure The residue
  5. customwas purified by column chromatography (using 60-120 silica gel and 50% EtOAc in hexane as eluent)

Sources & evidence

ORD record
ord-2873809a451549d597bcf8808026e09e
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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