1-Hydroxybenzotriazole → HCID 178523517, compound

HRID 1093726Notes

Reaction equation

HRID 1093726 reaction equation
CCN(C(C)C)C(C)C.[C:10]1([C:16]2[NH:20][N:19]=[C:18]([C:21]([OH:23])=O)[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.[NH2:47][CH2:48][C:49]([N:51]1[CH2:56][CH2:55][CH:54]([O:57][C:58]2[CH:63]=[C:62]([C:64]([F:67])([F:66])[F:65])[CH:61]=[CH:60][C:59]=2[F:68])[CH2:53][CH2:52]1)=[O:50]>CN(C=O)C.O>[F:68][C:59]1[CH:60]=[CH:61][C:62]([C:64]([F:65])([F:67])[F:66])=[CH:63][C:58]=1[O:57][CH:54]1[CH2:55][CH2:56][N:51]([C:49](=[O:50])[CH2:48][NH:47][C:21]([C:18]2[CH:17]=[C:16]([C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=3)[NH:20][N:19]=2)=[O:23])[CH2:52][CH2:53]1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 665915452-Amino-1-[4-(2-fluoro-5-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethanone hydrochlorideHCID 178524117HCID 178524117, compound

Product 1

HCID 178523517HCID 178523517, compoundYield 80.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (110 mg, 0.85 mmol) was added to a stirred solution of 5-phenyl-1H-pyrazole-3-carboxylic acid (50 mg, 0.24 mmol) in DMF (2 mL) followed by HOBt (33 mg, 0.24 mmol) and EDCI.HCl (49 mg, 0.25 mmol). After 2 minutes 2-amino-1-[4-(2-fluoro-5-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethanone hydrochloride (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 and dried over sodium sulfate. The organic layer was concentrated under reduced pressure to afford the residue. The residue obtained was purified by recrystallisation using 25% EtOAc in hexane to afford 89 mg (80.9% Yield) of 5-phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(2-fluoro-5-trifluoromethyl-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 457, 90.38%. 1H NMR (300 MHz, DMSO-d6): δ13.8 (s, 1H), 8.2 (bs, 1H), 7.9 (t, 1H), 7.1 (m, 7H), 4.61 (m, 1H), 4.4 (d, 2H), 3.7 (m, 2H), 3.3 (m, 2H), 1.9 (m, 2H), 1.5 (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 obtained
  7. customwas purified by recrystallisation

Sources & evidence

ORD record
ord-69fb7d085fc74b61b47af95513efed70
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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