1-Hydroxybenzotriazole → HCID 178523496, compound

HRID 1093729Notes

Reaction equation

HRID 1093729 reaction equation
CCN(C(C)C)C(C)C.[F:10][C:11]([F:27])([F:26])[C:12]1[CH:17]=[CH:16][C:15]([C:18]2[NH:22][N:21]=[C:20]([C:23]([OH:25])=O)[CH:19]=2)=[CH:14][CH:13]=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]=[CH:64][C:63]=2[Cl:68])[CH2:57][CH2:56]1)=[O:54]>CN(C=O)C.O>[Cl:68][C:63]1[CH:64]=[CH:65][CH:66]=[CH:67][C:62]=1[O:61][CH:58]1[CH2:57][CH2:56][N:55]([C:53](=[O:54])[CH2:52][NH:51][C:23]([C:20]2[CH:19]=[C:18]([C:15]3[CH:14]=[CH:13][C:12]([C:11]([F:10])([F:27])[F:26])=[CH:17][CH:16]=3)[NH:22][N:21]=2)=[O:25])[CH2:60][CH2:59]1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 665915282-Amino-1-[4-(2-chloro-phenoxy)-piperidin-1-yl]-ethanone hydrochlorideHCID 178524120HCID 178524120, compound

Product 1

HCID 178523496HCID 178523496, compoundYield 48.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (150 mg, 1.15 mmol) was added to a stirred solution of 5-(4-trifluoromethyl-phenyl)-1H-pyrazole-3-carboxylic acid (84 mg, 0.33 mmol) (prepared by the method used for the synthesis of Intermediate 29, starting from (p-trifluoromethyl)acetophenone) in DMF (2 mL) followed by HOBt (46 mg, 0.34 mmol) and EDCI.HCl (66 mg, 0.34 mmol). After 2 minutes 2-amino-1-[4-(2-chloro-phenoxy)-piperidin-1-yl]-ethanone hydrochloride (prepared according to Step 1 and 5 of the General Scheme) (100 mg, 0.33 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 mixture of ethyl acetate and methanol to afford 80 mg (48.2% Yield) of 5-(4-trifluoromethyl-phenyl)-1H-pyrazole-3-carboxylic acid {2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 507, 92.02%. 1H NMR (300 MHz, DMSO-d6): δ13.7 (d, 1H), 8.0 (m, 3H), 7.8 (m, 2H), 7.44 (d, 1H), 7.24 (m, 3H), 6.96 (m, 1H), 4.7 (m, 1H), 4.2 (d, 2H), 3.7 (m, 2H), 3.4 (m, 2H), 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 mixture of ethyl acetate and methanol

Sources & evidence

ORD record
ord-da9a075ded894397bf171ba3c86959dd
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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