Piperazin-2-one → HCID 50914333, compound

HRID 1942066Notes

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+].[NH:27]1[CH2:32][CH2:31][NH:30][CH2:29][C:28]1=[O:33]>CN1C(=O)CCC1.CCOC(C)=O>[F:24][C:14]1[C:13]([CH:11]([C:8]2[N:6]3[N:7]=[C:2]([N:30]4[CH2:31][CH2:32][NH:27][C:28](=[O:33])[CH2:29]4)[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

Conditions

Temperature: 180 °C

Procedure

(rac)-6-[1-(6-Chloro-imidazo[1,2-b]pyridazin-3-yl)-ethyl]-5,7-difluoro-quinoline (Intermediate C, 6.40 g, 18.21 mmol), KF (5.34 g, 91.0 mmol), piperazin-2-one (5.64 g, 54.6 mmol) were suspended in NMP (60 mL). The RM was stirred at 180° C. for 7 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 flash chromatography and then crystallized in DCM to afford the title compound as a beige solid (tR 3.02 min (conditions 1), (tR 7.58/10.54 min (conditions 3, MH+=409.1, 1H-NMR in DMSO-d6: 8.94 (d, 1H); 8.45 (d, 1H); 8.05 (s, 1H); 7.83 (d, 1H); 7.63 (m, 1H); 7.62 (s, 1H); 7.59 (m, 1H); 7.05 (d, 1H); 4.99 (m, 1H); 3.97 (d, 1H); 3.69 (d, 1H); 3.51 (m, 2H); 3.19 (m, 1H); 3.12 (m, 1H); 1.88 (d, 3H)).

Workup

washwashed with 1M Na2CO3 (1×) and water (2×)
extractionThe aqueous was further extracted with EtOAc (2×)
dry with materialThe combined organic layers were dried over Na2SO4
filtrationfiltered
concentrationconcentrated
customThe residue was purified by flash chromatography
customcrystallized in DCM

Sources & evidence

ORD record: ord-62001ec23a314df7bb15579b02b84b41
Source dataset: uspto-grants-2013_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08389526B2

Reaction notes

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