Diisopropylethylamine → HCID 49870875, compound

HRID 1942065Notes

Reaction equation

HRID 1942065 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C@H: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+].Cl.[CH3:28][N:29]1[CH2:34][CH2:33][NH:32][CH2:31][C:30]1=[O:35].C(N(C(C)C)C(C)C)C>CN1C(=O)CCC1.CCOC(C)=O>[F:24][C:14]1[C:13]([C@@H:11]([C:8]2[N:6]3[N:7]=[C:2]([N:32]4[CH2:33][CH2:34][N:29]([CH3:28])[C:30](=[O:35])[CH2:31]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

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 522689Potassium FluorideHCID 170607661-Methylpiperazin-2-one--hydrogen chloride (1/1)HCID 58147525HCID 58147525, compound2×

Product 1

HCID 49870875HCID 49870875, compound

Reagents, catalysts & solvents 2

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

Conditions

Temperature
180 °C

Procedure

6-[(S)-1-(6-chloro-imidazo[1,2-b]pyridazin-3-yl)-ethyl]-5,7-difluoro-quinoline (Intermediate B, 3.0 g, 8.58 mmol), KF (2.52 g, 42.9 mmol), 1-methylpiperazine-2-one hydrochloride (3.88 g, 25.7 mmol), N-ethyldiisopropylamine (5.99 mL, 35 mmol) were suspended in NMP (60 mL). The RM was stirred at 180° C. for 8.5 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 EtOAc to afford the title compound as a white solid (tR 3.19 min (conditions 1), (tR 8.84 min (conditions 2), MH+=423.2, 1H-NMR in DMSO-d6: 8.94 (d, 1H); 8.45 (d, 1H); 7.84 (d, 1H); 7.63 (s, 1H); 7.59 (m, 2H); 7.08 (d, 1H); 4.98 (m, 1H); 4.02 (d, 1H); 3.73 (d, 1H); 3.60 (m, 2H); 3.31 (m, 1H); 3.25 (m, 1H); 2.80 (s, 3H); 1.88 (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 flash chromatography
  7. customcrystallized in EtOAc

Sources & evidence

ORD record
ord-5da24e374d7047c5aa6793bebeaee1d3
Source dataset
uspto-grants-2013_03
Patent number
US08389526B2

Reaction notes

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