4'-Fluoroacetophenone → HCID 57874434, compound

HRID 1093763Notes

Reaction equation

HRID 1093763 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]([OH:24])=O)[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.[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:14]4[CH:13]=[CH:12][C:11]([F:10])=[CH:16][CH:15]=4)[O:21][N:20]=3)=[O:24])[CH2:67][CH2:66]2)[CH:70]=[N:71][CH:72]=1

Participants

9

Reactant 6

HCID 98284'-FluoroacetophenoneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 10963925-(4-Fluorophenyl)-1,2-oxazole-3-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 665916722-Amino-1-[4-(5-chloro-pyridin-3-yloxy)-piperidin-1-yl]-ethanone hydrochloride

Product 1

HCID 57874434HCID 57874434, compoundYield 17.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (253 mg, 1.96 mmol) was added to a stirred solution of 5-(4-fluoro-phenyl)-isoxazole-3-carboxylic acid (81 mg, 0.39 mmol) (prepared by the method used for the synthesis of Intermediate 25, starting from 4′-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. Purification by recrystallisation from 10% ethyl acetate in hexane afforded 32 mg (17.8% Yield) of 5-(4-fluoro-phenyl)-isoxazole-3-carboxylic acid {2-[4-(5-chloro-pyridin-3-yloxy)-piperidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 459, 92.84%. 1H NMR (300 MHz, CDCl3): δ8.2 (s, 2H), 7.86 (m, 1H), 7.76 (m, 2H), 7.14 (m, 3H), 6.9 (s, 1H), 4.7 (m, 1H), 4.3 (m, 2H), 3.7 (m, 3H), 3.5 (m, 1H), 1.9 (m, 4H).

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-06be809f76a448458447dc104b4d13f8
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

Loading…