3-Acetylpyridine → HCID 178523498, compound

HRID 1093746Notes

Reaction equation

HRID 1093746 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]=[CH:70][C:69]=2[Cl:74])[CH2:63][CH2:62]1)=[O:60]>CN(C=O)C.O>[Cl:74][C:69]1[CH:70]=[CH:71][CH:72]=[CH:73][C:68]=1[O:67][CH:64]1[CH2:63][CH2:62][N:61]([C:59](=[O:60])[CH2:58][NH:57][C:22]([C:19]2[CH:18]=[C:17]([C:13]3[CH:12]=[N:11][CH:16]=[CH:15][CH:14]=3)[NH:21][N:20]=2)=[O:24])[CH2:66][CH2:65]1

Participants

9

Reactant 6

HCID 95893-AcetylpyridineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 665915282-Amino-1-[4-(2-chloro-phenoxy)-piperidin-1-yl]-ethanone hydrochlorideHCID 1784797413-(3-Pyridinyl)-1H-pyrazole-5-carboxylic acid hydrochloride

Product 1

HCID 178523498HCID 178523498, compoundYield 51.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (290 mg, 2.26 mmol) to a stirred solution of 5-pyridin-3-yl-1H-pyrazole-3-carboxylic acid hydrochloride (100 mg, 0.44 mmol) (prepared by the method used for the synthesis of Intermediate 29, starting from 3-acetylpyridine) in DMF (2 mL) followed by HOBt (63 mg, 0.46 mmol) and EDCI.HCl (90 mg, 0.46 mmol). After 2 minutes 2-amino-1-[4-(2-chloro-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. Purification by recrystallisation from 10% EtOAc in hexane afforded 100 mg (51.5% Yield) of 5-pyridin-3-yl-1H-pyrazole-3-carboxylic acid {2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 440, 96.47%. 1H NMR (300 MHz, DMSO-d6): δ 13.9 (s, 1H), 9.0 (m, 1H), 8.5 (m, 1H), 8.1 (m, 2H), 7.4 (m, 2H), 7.2 (m, 3H), 6.9 (m, 1H), 4.75 (m, 1H), 4.2 (m, 2H), 3.65 (m, 2H), 3.4 (m, 2H), 1.9 (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. concentrationconcentrated under reduced pressure
  5. customPurification
  6. customby recrystallisation from 10% EtOAc in hexane

Sources & evidence

ORD record
ord-68971535dfff4c62ac47221c92b71a32
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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