1-Hydroxybenzotriazole → HCID 178523505, compound

HRID 1093732Notes

Reaction equation

HRID 1093732 reaction equation
CCN(C(C)C)C(C)C.[F:10][C:11]([F:27])([F:26])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[C:18]1[NH:22][N:21]=[C:20]([C:23]([OH:25])=O)[CH:19]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.[NH2:51][CH2:52][C:53]([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:54]>CN(C=O)C.O>[O:54]=[C:53]([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:71])([F:69])[F:70])[CH:63]=2)[CH2:59][CH2:60]1)[CH2:52][NH:51][C:23]([C:20]1[CH:19]=[C:18]([C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=2[C:11]([F:10])([F:27])[F:26])[NH:22][N:21]=1)=[O:25]

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 1785241123-(2-(trifluoromethyl)phenyl)-1H-pyrazole-5-carboxylic acid

Product 1

HCID 178523505HCID 178523505, compoundYield 56%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (76 mg, 0.59 mmol) was added to a stirred solution of 5-(2-trifluoromethyl-phenyl)-1H-pyrazole-3-carboxylic acid (43 mg, 0.167 mmol) (prepared by the method used for the synthesis of Intermediate 29, starting from (o-trifluoromethyl)acetophenone) in DMF (2 mL) followed by HOBt (24 mg, 0.176 mmol) and EDCI.HCl (34 mg, 0.176 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) (0.057 mg, 0.167 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 chloroform to afford 51 mg (56% Yield) of 5-(2-trifluoromethyl-phenyl)-1H-pyrazole-3-carboxylic acid {2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide. LC/MS [M+H]+: 541, 87.52%. 1H NMR (300 MHz, DMSO-d6): δ13.8 (d, 1H), 8.1 (m, 1H), 7.6 (m, 4H), 7.5 (t, 1H), 7.3 (t, 3H), 6.76 (s, 1H), 4.8 (m, 1H), 4.1 (d, 2H), 3.7 (m, 2H), 3.4 (m, 1H), 3.2 (m, 1H), 1.9 (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. concentrationThe organic layer was concentrated under reduced pressure
  6. customto afford the residue
  7. customThe residue was purified
  8. washby washing with chloroform

Sources & evidence

ORD record
ord-f2139c56c01544bb8061e511fdf4471a
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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