4'-Fluoroacetophenone → HCID 57874463, compound

HRID 1093764Notes

Reaction equation

HRID 1093764 reaction equation
CCN(C(C)C)C(C)C.[F:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[O:21][N:20]=[C:19]([C:22]([NH:24][CH2:25][C:26]([OH:28])=O)=[O:23])[CH:18]=2)=[CH:13][CH:12]=1.FC1C=CC(C(=O)C)=CC=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.[Cl:62][C:63]1[C:68]([O:69][CH:70]2[CH2:75][CH2:74][NH:73][CH2:72][CH2:71]2)=[CH:67][CH:66]=[CH:65][N:64]=1>CN(C=O)C.O>[Cl:62][C:63]1[C:68]([O:69][CH:70]2[CH2:75][CH2:74][N:73]([C:26](=[O:28])[CH2:25][NH:24][C:22]([C:19]3[CH:18]=[C:17]([C:14]4[CH:13]=[CH:12][C:11]([F:10])=[CH:16][CH:15]=4)[O:21][N:20]=3)=[O:23])[CH2:72][CH2:71]2)=[CH:67][CH:66]=[CH:65][N:64]=1

Participants

9

Reactant 6

HCID 98284'-FluoroacetophenoneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 46735697HCID 46735697, compoundHCID 66591887HCID 66591887, compound

Product 1

HCID 57874463HCID 57874463, compoundYield 50%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (186 mg, 1.43 mmol) was added to a stirred solution of {[5-(4-fluoro-phenyl)-isoxazole-3-carbonyl]-amino}-acetic acid (76 mg, 0.29 mmol) (prepared by the method used for the synthesis of Intermediate 26, starting from 4′-fluoroacetophenone) in DMF (2 mL) followed by HOBt (41 mg, 0.3 mmol) and EDCI.HCl (58 mg, 0.3 mmol). After 2 minutes 2-chloro-3-(piperidin-4-yloxy)-pyridine hydrochloride (72 mg, 0.29 mmol) (prepared by method used for the synthesis of Intermediate 15) 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% ethyl acetate in hexane to afford 66 mg (50% Yield) of 5-(4-fluoro-phenyl)-isoxazole-3-carboxylic acid {2-[4-(2-chloro-pyridin-3-yloxy)-piperidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 459, 94.53%. 1H NMR (300 MHz, DMSO-d6): δ 8.65 (s, 1H), 7.98 (m, 3H), 7.72 (m, 1H), 7.38 (m, 4H), 4.8 (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. concentrationconcentrated under reduced pressure
  6. customPurification
  7. customby recrystallisation from 10% ethyl acetate in hexane

Sources & evidence

ORD record
ord-1d0545e6cf8149069995329eb1431c3e
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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