1-Hydroxybenzotriazole → HCID 178523507, compound

HRID 1093712Notes

Reaction equation

HRID 1093712 reaction equation
CCN(C(C)C)C(C)C.[C:10]1([C:16]2[NH: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.NCC([N:55]1[CH2:60][CH2:59][CH:58]([O:61][C:62]2[CH:67]=[CH:66][CH:65]=[C:64]([C:68]([F:71])([F:70])[F:69])[CH:63]=2)[CH2:57][CH2:56]1)=O>CN(C=O)C.O>[O:27]=[C:25]([N:55]1[CH2:56][CH2:57][CH:58]([O:61][C:62]2[CH:67]=[CH:66][CH:65]=[C:64]([C:68]([F:69])([F:70])[F:71])[CH:63]=2)[CH2:59][CH2:60]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)[NH:20][N:19]=1)=[O:22]

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 665915472-Amino-1-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethanone hydrochlorideHCID 178525878HCID 178525878, compound

Product 1

HCID 178523507HCID 178523507, compoundYield 16.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (360 mg, 2.8 mmol) was added to a stirred solution of [(5-phenyl-1H-pyrazole-3-carbonyl)-amino]-acetic acid (200 mg, 0.8 mmol) in DMF (2 mL) followed by HOBt (131 mg, 0.97 mmol) and EDCI.HCl (187 mg, 00.97 mmol). After 2 minutes of stirring, 2-amino-1-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethanone hydrochloride (prepared according to Step 1 and 5 of the General Scheme) (200 mg, 0.8 mmol) was added 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. Purification by column chromatography (using neutral alumina and 5% MeOH in CHCl3 as eluent) to afford 62 mg (16.2% Yield) of 5-phenyl-1H-pyrazole-3-carboxylic acid {2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide. LC/MS [M+H]+: 473.17, 91%, 1H NMR (300 MHz, DMSO-d6): δ8.1 (m, 1H), 7.8 (d, 2H), 7.5 (m, 3H), 7.4 (m, 4H), 7.1 (s, 1H), 4.8 (m, 1H), 4.2 (d, 2H), 3.8 (m, 1H), 3.6 (m, 1H), 3.5 (m, 2H), 2.0 (m, 2H), 1.6 (m, 2H).

Workup

  1. additionwas added
  2. stirringstirring
  3. waitwas continued at ambient temperature overnight
  4. extractionextracted with ethyl acetate
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customPurification by column chromatography (using neutral alumina and 5% MeOH in CHCl3 as eluent)

Sources & evidence

ORD record
ord-24c8ae0a14774f7aafde72d03c0beb73
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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