3-Acetylpyridine → HCID 178523513, compound

HRID 1093745Notes

Reaction equation

HRID 1093745 reaction equation
CCN(C(C)C)C(C)C.Cl.[N:11]1[CH:16]=[CH:15][CH:14]=[C:13]([C:17]2[NH:21][N:20]=[C:19]([C:22]([OH:24])=O)[CH:18]=2)[CH:12]=1.C(C1C=NC=CC=1)(=O)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.[NH2:57][CH2:58][C:59]([N:61]1[CH2:66][CH2:65][CH:64]([O:67][C:68]2[CH:73]=[CH:72][CH:71]=[C:70]([C:74]([F:77])([F:76])[F:75])[CH:69]=2)[CH2:63][CH2:62]1)=[O:60]>CN(C=O)C.O>[O:60]=[C:59]([N:61]1[CH2:62][CH2:63][CH:64]([O:67][C:68]2[CH:73]=[CH:72][CH:71]=[C:70]([C:74]([F:77])([F:75])[F:76])[CH:69]=2)[CH2:65][CH2:66]1)[CH2:58][NH:57][C:22]([C:19]1[CH:18]=[C:17]([C:13]2[CH:12]=[N:11][CH:16]=[CH:15][CH:14]=2)[NH:21][N:20]=1)=[O:24]

Participants

9

Reactant 6

HCID 95893-AcetylpyridineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 665915472-Amino-1-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethanone hydrochlorideHCID 1784797413-(3-Pyridinyl)-1H-pyrazole-5-carboxylic acid hydrochloride

Product 1

HCID 178523513HCID 178523513, compoundYield 66%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (290 mg, 2.26 mmol) was added to a stirred solution of 5-pyridin-3-yl-1H-pyrazole-3-carboxylic acid hydrochloride (prepared by the method used for the synthesis of Intermediate 29, starting from 3-acetylpyridine) (100 mg, 0.44 mmol) in DMF (2 mL) followed by HOBt (63 mg, 0.46 mmol) and EDCI.HCl (90 mg, 0.46 mmol). After 5 minutes 2-amino-1-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethanone hydrochloride (150 mg, 0.44 mmol) (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, dried over sodium sulfate and concentrated under reduced pressure The residue was purified by filtering through 60-120 silica gel column and filtrate collected was concentrated under reduced pressure to afford 138 mg (66% Yield) of 5-pyridin-3-yl-1H-pyrazole-3-carboxylic acid {2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide. LC/MS [M+H]+: 474, 94.7%. 1H NMR (300 MHz, DMSO-d6): δ 13.8 (s, 1H), 9.4 (s, 1H), 8.56 (d, 1H), 8.16 (m, 1H), 7.46 (m, 2H), 7.22 (m, 4H), 4.8 (m, 1H), 4.2 (d, 2H), 3.9 (m, 1H), 3.7 (m, 1H), 3.44 (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. concentrationconcentrated under reduced pressure The residue
  6. customwas purified
  7. filtrationby filtering through 60-120 silica gel column and filtrate
  8. customcollected
  9. concentrationwas concentrated under reduced pressure

Sources & evidence

ORD record
ord-e098ea6551c749ab85bbdea66b984d6e
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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