N-methyl-2-pyrrolidone → (rac)-4-{3-[1-(5,7-Difluoro-quinolin-6-yl)-ethyl]-imidazo[1,2-b]pyridazin-6-yl}-3-methyl-piperazin-2-one

HRID 1942075Notes

Reaction equation

HRID 1942075 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:24])=[C:15]4[C:20](=[CH:21][C:22]=3[F:23])[N:19]=[CH:18][CH:17]=[CH:16]4)[CH3:12])=[CH:9][N:10]=2)[N:7]=1.[F-].[K+].[CH3:27][CH:28]1[NH:33][CH2:32][CH2:31][NH:30][CH2:29]1.CN1C(=[O:40])CCC1>>[F:24][C:14]1[C:13]([CH:11]([C:8]2[N:6]3[N:7]=[C:2]([N:33]4[CH2:32][CH2:31][NH:30][C:29](=[O:40])[CH:28]4[CH3:27])[CH:3]=[CH:4][C:5]3=[N:10][CH:9]=2)[CH3:12])=[C:22]([F:23])[CH:21]=[C:20]2[C:15]=1[CH:16]=[CH:17][CH:18]=[N:19]2

Participants

5

Reactant 4

HCID 13387N-methyl-2-pyrrolidoneHCID 660572-MethylpiperazineHCID 522689Potassium FluorideHCID 58147541(Rac)-6-[1-(6-chloro-imidazo[1,2-b]pyridazin-3-yl)-ethyl]-5,7-difluoro-quinoline2×

Product 1

HCID 50914631(rac)-4-{3-[1-(5,7-Difluoro-quinolin-6-yl)-ethyl]-imidazo[1,2-b]pyridazin-6-yl}-3-methyl-piperazin-2-one

Conditions

Temperature
180 °C

Procedure

(rac)-6-[1-(6-Chloro-imidazo[1,2-b]pyridazin-3-yl)-ethyl]-5,7-difluoro-quinoline (Intermediate C, 55 mg, 0.160 mmol), KF (46.3 mg, 0.798 mmol), 3-methylpiperazine (54.6 mg, 0.479 mmol) were suspended in NMP (532 μL). The RM was stirred at 180° C. for 16 h. The mixture was purified by preparative UPLC with acetonitrile and water (+0.1% TFA) The fractions were collected and acetonitrile was removed. It was taken up with EtOAc/MeOH (9/1) and washed with 5% Na2CO3 solution and brine. The organic layer was dried over sodium sulfate and the solvent was removed. A brown solid was obtained (tR 0.9 min (conditions 4), MH+=423)

Workup

  1. customThe mixture was purified by preparative UPLC with acetonitrile and water (+0.1% TFA) The fractions
  2. customwere collected
  3. customacetonitrile was removed
  4. washwashed with 5% Na2CO3 solution and brine
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. customthe solvent was removed
  7. customA brown solid was obtained (tR 0.9 min (conditions 4), MH+=423)

Sources & evidence

ORD record
ord-dda4ac70bf5f4c94808511d445beb1bb
Source dataset
uspto-grants-2013_03
Patent number
US08389526B2

Reaction notes

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