3-Fluoroacetophenone → HCID 178523527, compound

HRID 1093740Notes

Reaction equation

HRID 1093740 reaction equation
CCN(C(C)C)C(C)C.[F:10][C:11]1[CH:12]=[C:13]([C:17]2[NH:21][N:20]=[C:19]([C:22]([OH:24])=O)[CH:18]=2)[CH:14]=[CH:15][CH:16]=1.FC1C=C(C(=O)C)C=CC=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.[NH2:58][CH2:59][C:60]([N:62]1[CH2:67][CH2:66][CH:65]([O:68][C:69]2[CH:70]=[N:71][CH:72]=[C:73]([Cl:75])[CH:74]=2)[CH2:64][CH2:63]1)=[O:61]>CN(C=O)C.O>[Cl:75][C:73]1[CH:74]=[C:69]([O:68][CH:65]2[CH2:64][CH2:63][N:62]([C:60](=[O:61])[CH2:59][NH:58][C:22]([C:19]3[CH:18]=[C:17]([C:13]4[CH:14]=[CH:15][CH:16]=[C:11]([F:10])[CH:12]=4)[NH:21][N:20]=3)=[O:24])[CH2:67][CH2:66]2)[CH:70]=[N:71][CH:72]=1

Participants

9

Reactant 6

HCID 99673-FluoroacetophenoneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 665916722-Amino-1-[4-(5-chloro-pyridin-3-yloxy)-piperidin-1-yl]-ethanone hydrochlorideHCID 178524119HCID 178524119, compound

Product 1

HCID 178523527HCID 178523527, compoundYield 43.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (253 mg, 1.96 mmol) was added to a stirred solution of 5-(3-fluoro-phenyl)-1H-pyrazole-3-carboxylic acid (81 mg, 0.39 mmol) (prepared by the method used for the synthesis of Intermediate 29, starting from 3′-fluoroacetophenone) in DMF (2 mL) followed by HOBt (56 mg, 0.41 mmol) and EDCI.HCl (79 mg, 0.41 mmol). After 2 minutes 2-amino-1-[4-(5-chloro-pyridin-3-yloxy)-piperidin-1-yl]-ethanone hydrochloride (120 mg, 0.39 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 washing with ethyl acetate to afford 78 mg (43.5% Yield) of 5-(3-fluoro-phenyl)-1H-pyrazole-3-carboxylic acid {2-[4-(5-chloro-pyridin-3-yloxy)-piperidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 458, 90%. 1H NMR (300 MHz, DMSO-d6): δ 13.8 (s, 1H), 8.3 (d, 1H), 8.22 (d, 1H), 8.04 (m, 1H), 7.6 (m, 3H), 7.5 (m, 2H), 7.18 (m, 2H), 4.8 (m, 1H), 4.2 (m, 2H), 3.9 (m, 1H), 3.7 (m, 1H), 3.4 (m, 1H), 3.2 (m, 1H), 2.0 (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. washby washing with ethyl acetate

Sources & evidence

ORD record
ord-3b7a6addb16e4cd0a57e8f6d3a366665
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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