3-Chloroaniline → (3-Chloro-phenyl)-(3-quinolin-6-ylmethyl-imidazo[1,2-b]pyridazin-6-yl)-amine

HRID 69178Notes

Reaction equation

HRID 69178 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:5]=[C:6]([CH:8]=[CH:9][CH:10]=1)[NH2:7].Cl[C:12]1[CH:13]=[CH:14][C:15]2[N:16]([C:18]([CH2:21][C:22]3[CH:23]=[C:24]4[C:29](=[CH:30][CH:31]=3)[N:28]=[CH:27][CH:26]=[CH:25]4)=[CH:19][N:20]=2)[N:17]=1>CN1C(=O)CCC1.CCOC(C)=O>[Cl:3][C:4]1[CH:5]=[C:6]([NH:7][C:12]2[CH:13]=[CH:14][C:15]3[N:16]([C:18]([CH2:21][C:22]4[CH:23]=[C:24]5[C:29](=[CH:30][CH:31]=4)[N:28]=[CH:27][CH:26]=[CH:25]5)=[CH:19][N:20]=3)[N:17]=2)[CH:8]=[CH:9][CH:10]=1

Participants

6

Reactant 3

HCID 79323-ChloroanilineHCID 24758Sodium hydrideHCID 579174466-(6-Chloro-imidazo[1,2-b]pyridazin-3-ylmethyl)-quinoline

Product 1

HCID 57917421(3-Chloro-phenyl)-(3-quinolin-6-ylmethyl-imidazo[1,2-b]pyridazin-6-yl)-amine

Reagents, catalysts & solvents 2

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

Conditions

Temperature
85 °C

Procedure

NaH (34 mg, 0.85 mmol) was suspended in NMP (1.5 mL) under argon. 3-Chloroaniline (108 μL, 1.017 mmol) was added and the RM was heated to 85° C. After 10 min, 6-(6-chloro-imidazo[1,2-b]pyridazin-3-ylmethyl)-quinoline (Example 14, 100 mg, 0.339 mmol) was added and the RM was stirred at 85° C. for 1 h. The mixture was then heated to 160° C. for 10 min. The mixture was diluted with EtOAc and washed with water (3×). The aqueous layer was extracted with EtOAc (3×). The combined organic layers were dried over Na2SO4, filtered and concentrated. The residue was purified by flash chromatography (Flashmaster) and crystallized in Et2O to afford the title compound as a yellow solid (tR 4.99 min (conditions 4), MH+=386.1, 1H-NMR in DMSO-d6: 9.57 (s, 1H); 8.82 (m, 1H); 7.93 (m, 3H); 7.86 (m, 1H); 7.71 (m, 1H); 7.56 (s, 1H); 7.47 (dd, 1H); 7.43 (m, 1H); 7.25 (t, 1H); 6.99 (m, 1H); 6.85 (d, 1H); 4.50 (s, 2H)).

Workup

  1. temperatureThe mixture was then heated to 160° C. for 10 min
  2. washwashed with water (3×)
  3. extractionThe aqueous layer was extracted with EtOAc (3×)
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by flash chromatography (Flashmaster)
  8. customcrystallized in Et2O

Sources & evidence

ORD record
ord-cd475467ff3c4021bc12d1c53ae6a55d
Source dataset
uspto-grants-2014_09
Patent number
US08822468B2

Reaction notes

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