1-Hydroxybenzotriazole → HCID 178523514, compound

HRID 1093733Notes

Reaction equation

HRID 1093733 reaction equation
CCN(C(C)C)C(C)C.[OH:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[NH:21][N:20]=[C:19]([C:22]([OH:24])=O)[CH:18]=2)=[CH:13][CH:12]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.[NH2:48][CH2:49][C:50]([N:52]1[CH2:57][CH2:56][CH:55]([O:58][C:59]2[CH:64]=[CH:63][CH:62]=[C:61]([C:65]([F:68])([F:67])[F:66])[CH:60]=2)[CH2:54][CH2:53]1)=[O:51]>CN(C=O)C.O>[O:51]=[C:50]([N:52]1[CH2:53][CH2:54][CH:55]([O:58][C:59]2[CH:64]=[CH:63][CH:62]=[C:61]([C:65]([F:68])([F:66])[F:67])[CH:60]=2)[CH2:56][CH2:57]1)[CH2:49][NH:48][C:22]([C:19]1[CH:18]=[C:17]([C:14]2[CH:13]=[CH:12][C:11]([OH:10])=[CH:16][CH:15]=2)[NH:21][N:20]=1)=[O:24]

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 178524130HCID 178524130, compound

Product 1

HCID 178523514HCID 178523514, compoundYield 55%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (150 mg, 1.2 mmol) was added to a stirred solution of 5-(4-hydroxy-phenyl)-1H-pyrazole-3-carboxylic acid (70 mg, 0.34 mmol) in DMF (2 mL) followed by HOBt (48 mg, 0.36 mmol) and EDCI.HCl (69 mg, 0.36 mmol). After 2 minutes 2-amino-1-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethanone hydrochloride (prepared according to Step 1 and 5 of the General Scheme) (116 mg, 0.34 mmol) 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 and dried over sodium sulfate. The organic layer was concentrated under reduced pressure to afford the residue. The residue was purified by washing with 1% MeOH in EtOAc to afford 92 mg (55% Yield) of 5-(4-hydroxy-phenyl)-1H-pyrazole-3-carboxylic acid {2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide. LC/MS [M+H]+: 489, 96%. 1H NMR (300 MHz, DMSO-d6): δ13.8 (s, 1H), 9.8 (s, 1H), 8.02 (t, 1H), 7.5 (m, 3H), 7.28 (t, 3H), 6.8 (m, 3H), 4.8 (m, 1H), 4.2 (d, 2H), 3.9 (m, 1H), 3.6 (m, 1H), 3.4 (m, 1H), 3.2 (m, 1H), 2.0 (m, 2H), 1.7 (m, 2H).

Workup

  1. additionwas added to the reaction mixture
  2. extractionextracted with ethyl acetate
  3. dry with materialdried over sodium sulfate
  4. concentrationThe organic layer was concentrated under reduced pressure
  5. customto afford the residue
  6. customThe residue was purified
  7. washby washing with 1% MeOH in EtOAc

Sources & evidence

ORD record
ord-0e25d1f362c141ffbb57df4a9ce4a818
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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