2-Acetylpyridine → HCID 178523497, compound

HRID 1093743Notes

Reaction equation

HRID 1093743 reaction equation
CCN(C(C)C)C(C)C.Cl.[N:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[C:17]1[NH:21][N:20]=[C:19]([C:22]([OH:24])=O)[CH:18]=1.C(C1C=CC=CN=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:12]3[CH:13]=[CH:14][CH:15]=[CH:16][N:11]=3)[NH:21][N:20]=2)=[O:24])[CH2:66][CH2:65]1

Participants

9

Reactant 6

HCID 142862-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 178479740HCID 178479740, compound

Product 1

HCID 178523497HCID 178523497, compoundYield 74.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (287 mg, 2.2 mmol) was added to a stirred solution of 5-pyridin-2-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 2-acetylpyridine) in DMF (2 mL) followed by HOBt (63 mg, 0.46 mmol) and EDCI.HCl (89 mg, 0.46 mmol). After 2 minutes 2-amino-1-[4-(2-chloro-phenoxy)-piperidin-1-yl]-ethanone hydrochloride (135 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 145 mg (74.3% Yield) of 5-pyridin-2-yl-1H-pyrazole-3-carboxylic acid {2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 440, 90%. 1H NMR (300 MHz, DMSO-d6): δ 13.9 (s, 1H), 8.6 (d, 1H), 8.1 (bs, 1H), 7.84 (m, 2H), 7.24 (m, 5H), 6.94 (m, 2H), 4.75 (m, 1H), 4.15 (d, 2H), 3.6 (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. 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-3803f025aa574ddabc9fb144b922db8b
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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