Piperazin-2-one → HCID 50914921, compound

HRID 1942083Notes

Reaction equation

HRID 1942083 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH: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.CCOC(C)=O>[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[CH: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 581475176-Chloro-3-(1-(6-fluoro-1-methyl-1H-indazol-5-yl)ethyl)imidazo[1,2-b]pyridazine2×

Product 1

HCID 50914921HCID 50914921, compound

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
180 °C

Procedure

(rac)-6-Chloro-3-[1-(6-fluoro-1-methyl-1H-indazol-5-yl)-ethyl]-imidazo[1,2-b]pyridazine (Intermediate G, 100 mg, 0.303 mmol), KF (88 mg, 1.5 mmol), piperazin-2-one (91 mg, 0.91 mmol) were suspended in NMP (1 mL). The RM was stirred at 180° C. for 2 h. The mixture was diluted with EtOAc and washed with 1M Na2CO3 (1×) and water (2×). The aqueous was further extracted with EtOAc (2×). The combined organic layers were dried over Na2SO4, filtered and concentrated. The residue was purified by preparative UPLC with acetonitrile and water (+0.1% TFA). The fractions were joined and were lyophilized. The residue was dissolved in MeOH and it was passed through an SPE cartridge of HCO3 to remove the TFA salt. The filtrate was evaporated and the residue was triturated with pentane. The precipitate was filtered off and dried to afford the title compound as a white solid (tR 0.88 min (conditions 4), MH+=394, 1H-NMR in DMSO-d6: 8.10 (br. s, 1H); 7.95-7.87 (m, 2H); 7.65 (s, 1H); 7.51 (s, 1H); 7.54 (d, 1H); 7.49 (s, 1H); 7.22 (d, 1H); 4.79 (q, 1H); 3.95 (s, 4H); 3.87-3.78 (m, 1H); 3.67-3.55 (m, 2H); 3.22 (dd, 1H); 3.29-3.14 (m, 1H); 1.71 (d, 3H)).

Workup

  1. washwashed with 1M Na2CO3 (1×) and water (2×)
  2. extractionThe aqueous was further extracted with EtOAc (2×)
  3. dry with materialThe combined organic layers were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by preparative UPLC with acetonitrile and water (+0.1% TFA)
  7. dissolutionThe residue was dissolved in MeOH
  8. customto remove the TFA salt
  9. customThe filtrate was evaporated
  10. customthe residue was triturated with pentane
  11. filtrationThe precipitate was filtered off
  12. customdried

Sources & evidence

ORD record
ord-0819ed0719ee49ac96d9717c9945626f
Source dataset
uspto-grants-2013_03
Patent number
US08389526B2

Reaction notes

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