Piperazin-2-one → HCID 50914922, compound

HRID 1942084Notes

Reaction equation

HRID 1942084 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C@H:11]([C:13]3[CH:14]=[C:15]4[C:19](=[CH:20][C:21]=3[F:22])[N:18]([CH3:23])[N:17]=[CH:16]4)[CH3:12])=[CH:9][N:10]=2)[N:7]=1.[F-].[K+].[NH:26]1[CH2:31][CH2:30][NH:29][CH2:28][C:27]1=[O:32]>CN1C(=O)CCC1.CC#N>[F:22][C:21]1[CH:20]=[C:19]2[C:15]([CH:16]=[N:17][N:18]2[CH3:23])=[CH:14][C:13]=1[C@@H:11]([C:8]1[N:6]2[N:7]=[C:2]([N:29]3[CH2:30][CH2:31][NH:26][C:27](=[O:32])[CH2:28]3)[CH:3]=[CH:4][C:5]2=[N:10][CH:9]=1)[CH3:12]

Participants

6

Reactant 3

HCID 231360Piperazin-2-oneHCID 522689Potassium FluorideHCID 58147538HCID 58147538, compound2×

Product 1

HCID 50914922HCID 50914922, compound

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
180 °C

Procedure

6-Chloro-3-[(S)-1-(6-fluoro-1-methyl-1H-indazol-5-yl)-ethyl]-imidazo[1,2-b]pyridazine (Intermediate E, 66.0 mg, 0.2 mmol), KF (59.3 mg, 1.0 mmol) and piperazin-2-one (61.9 mg, 0.6 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: 5-24% 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 to afford the title compound as a yellow foam (tR 3.53 min (conditions 4), (tR 8.25 (conditions 5), MH+=394.3, 1H-NMR in DMSO-d6: 8.04 (s, 1H); 7.92 (s, 1H); 7.81 (d, 1H); 7.50 (m, 1H); 7.46 (d, 1H); 7.06 (d, 1H); 4.78 (m, 1H); 3.95 (s, 3H); 3.95 (d, 1H); 3.80 (d, 1H); 3.58 (m, 2H); 3.22 (m, 2H); 1.71 (d, 3H)).

Workup

  1. custompurified by reverse phase chromatography (Büchi MPLC: 5-24% CH3CN, 0.1% HCOOH)
  2. concentrationconcentrated
  3. extractionextracted with EtOAc
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-53486184b0c045b7bcf3b56b9818764f
Source dataset
uspto-grants-2013_03
Patent number
US08389526B2

Reaction notes

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