3-Fluoroacetophenone → HCID 178523483, compound

HRID 1093731Notes

Reaction equation

HRID 1093731 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]([NH:68][C:69]2[CH:74]=[CH:73][CH:72]=[CH:71][C:70]=2[Cl:75])[CH2:64][CH2:63]1)=[O:61]>CN(C=O)C.O>[Cl:75][C:70]1[CH:71]=[CH:72][CH:73]=[CH:74][C:69]=1[NH:68][CH:65]1[CH2:64][CH2:63][N:62]([C:60](=[O:61])[CH2:59][NH:58][C:22]([C:19]2[CH:18]=[C:17]([C:13]3[CH:14]=[CH:15][CH:16]=[C:11]([F:10])[CH:12]=3)[NH:21][N:20]=2)=[O:24])[CH2:67][CH2:66]1

Participants

9

Reactant 6

HCID 99673-FluoroacetophenoneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 665915702-Amino-1-[4-(2-chloro-phenylamino)-piperidin-1-yl]-ethanone hydrochlorideHCID 178524119HCID 178524119, compound

Product 1

HCID 178523483HCID 178523483, compoundYield 46.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (165 mg, 1.3 mmol) was added to a stirred solution of 5-(3-fluoro-phenyl)-1H-pyrazole-3-carboxylic acid (75 mg, 0.36 mmol) (prepared by the method used for the synthesis of Intermediate 29, starting from 3′-fluoroacetophenone) in DMF (2 mL) followed by HOBt (51 mg, 0.38 mmol) and EDCI.HCl (73 mg, 0.38 mmol). After 2 minutes 2-amino-1-[4-(2-chloro-phenylamino)-piperidin-1-yl]-ethanone hydrochloride (120 mg, 0.36 mmol) 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 and dried over sodium sulfate. The organic layer was concentrated under reduced pressure to afford the residue. Washing with methanol afforded 76 mg (43.1% Yield) of 5-(3-fluoro-phenyl)-1H-pyrazole-3-carboxylic acid {2-[4-(2-chloro-phenylamino)-piperidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 456, 100%. 1H NMR (300 MHz, DMSO-d6): δ13.8 (s, 1H), 8.06 (t, 1H), 7.44 (m, 4H), 7.12 (m, 4H), 6.84 (d, 1H), 6.58 (m, 1H), 4.9 (d, 1H), 4.3 (d, 1H), 4.2 (m, 2H), 3.7 (m, 1H), 3.6 (m, 1H), 3.2 (m, 1H), 2.8 (m, 1H), 1.9 (m, 2H), 1.4 (m, 2H).

Workup

  1. customprepared by the method
  2. extractionextracted with ethyl acetate
  3. dry with materialdried over sodium sulfate
  4. concentrationThe organic layer was concentrated under reduced pressure
  5. customto afford the residue
  6. washWashing with methanol

Sources & evidence

ORD record
ord-d825dee491fe4d93a988f3a0c55c212d
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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