Piperazin-2-one → HCID 50913306, compound

HRID 1942100Notes

Reaction equation

HRID 1942100 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH:11]([C:13]3[C:14]([F:26])=[C:15]4[C:19](=[CH:20][C:21]=3[F:22])[N:18]([CH:23]([CH3:25])[CH3:24])[N:17]=[CH:16]4)[CH3:12])=[CH:9][N:10]=2)[N:7]=1.[F-].[K+].[NH:29]1[CH2:34][CH2:33][NH:32][CH2:31][C:30]1=[O:35]>CN1C(=O)CCC1.CC#N>[F:26][C:14]1[C:13]([CH:11]([C:8]2[N:6]3[N:7]=[C:2]([N:32]4[CH2:33][CH2:34][NH:29][C:30](=[O:35])[CH2:31]4)[CH:3]=[CH:4][C:5]3=[N:10][CH:9]=2)[CH3:12])=[C:21]([F:22])[CH:20]=[C:19]2[C:15]=1[CH:16]=[N:17][N:18]2[CH:23]([CH3:25])[CH3:24]

Participants

6

Reactant 3

HCID 231360Piperazin-2-oneHCID 522689Potassium FluorideHCID 58147520HCID 58147520, compound2×

Product 1

HCID 50913306HCID 50913306, compound

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
180 °C

Procedure

(rac)-6-chloro-3-(1-(4,6-difluoro-1-isopropyl-1H-indazol-5-yl)ethyl)imidazo[1,2-b]pyridazine (Intermediate U, 56.4 mg, 0.15 mmol), KF (44.5 mg, 0.75 mmol) and piperazin-2-one (46.4 mg, 0.45 mmol) were suspended in NMP (0.5 mL). The RM was stirred at 180° C. for 3 h. The mixture was diluted with CH3CN and purified by reverse phase chromatography (Büchi MPLC: 5-28% CH3CN, 0.1% HCOOH). The fractions was combined, concentrated and neutralized with NaHCO3, extracted with EtOAc. The combined organics layers were tried over Na2SO4, filtered, concentrated, crystallized in EtOAc to afford the title compound as a white solid (tR 3.98 min (conditions 5), MH+=440.3, 1H-NMR in DMSO-d6: 8.09 (s, 1H); 7.80 (d, 1H); 7.53 (s, 1H); 7.41 (d, 1H); 7.05 (d, 1H), 4.86 (m, 2H); 4.03 (d, 1H); 3.74 (d, 1H); 3.54 (d, 2H); 3.17 (m, 2H); 1.79 (d, 3H); 1.41 (m, 6H)).

Workup

  1. custompurified by reverse phase chromatography (Büchi MPLC: 5-28% CH3CN, 0.1% HCOOH)
  2. concentrationconcentrated
  3. extractionextracted with EtOAc
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customcrystallized in EtOAc

Sources & evidence

ORD record
ord-8a523ca1208046f89b9937b299ebf6e6
Source dataset
uspto-grants-2013_03
Patent number
US08389526B2

Reaction notes

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