1,2-Dimethoxyethane → 2-Chloro-4-(3-quinolin-6-ylmethyl-imidazo[1,2-b]pyridazin-6-yl)-benzamide

HRID 69170Notes

Reaction equation

HRID 69170 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:11]3[CH:20]=[CH:19][C:18]4[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=4)[N:12]=3)=[CH:9][N:10]=2)[N:7]=1.[C:21]([C:24]1[CH:29]=[CH:28][C:27](B(O)O)=[CH:26][C:25]=1[Cl:33])(=[O:23])[NH2:22].[CH3:34]OCCOC.C([O-])([O-])=O.[Na+].[Na+]>C(Cl)Cl.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CN(C=O)C>[Cl:33][C:25]1[CH:26]=[C:27]([C:2]2[CH:3]=[CH:4][C:5]3[N:6]([C:8]([CH2:11][C:20]4[CH:19]=[C:18]5[C:13](=[CH:14][CH:15]=4)[N:12]=[CH:34][CH:16]=[CH:17]5)=[CH:9][N:10]=3)[N:7]=2)[CH:28]=[CH:29][C:24]=1[C:21]([NH2:22])=[O:23]

Participants

8

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 44119639(4-Carbamoyl-3-chlorophenyl)boronic acidHCID 44206294(6-Chloro-imidazo[1,2-b]pyridazin-3-yl)-quinoline

Product 1

HCID 442062952-Chloro-4-(3-quinolin-6-ylmethyl-imidazo[1,2-b]pyridazin-6-yl)-benzamide

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
90 °C

Procedure

A microwave tube was charged with (6-chloro-imidazo[1,2-b]pyridazin-3-yl)-quinoline (Example 14, 150 mg, 0.509 mmol), 4-carbamoyl-3-chlorophenyboronic acid (304 mg, 1.527 mmol), DME (1.6 mL) and DMF (250 μL). 2 M Na2CO3 (763 μL, 1.527 mmol) was then added, followed by tetrakis-(triphenylphosphine)-palladium (21 mg, 0.025 mmol). The RM was heated at 90° C. for 24 h. The cool reaction mixture was poured in DCM, filtered through a Celite pad and washed with water. The organic layer was dried over Na2SO4, filtered and concentrated in vacuo. While concentrating some crystals appeared. The crystals were filtered off and dried to afford the title compound as a beige solid (tR 4.28 min (conditions 4), MH+=414.4, 1H-NMR in DMSO-d6: 8.85 (m, 1H); 8.32 (m, 1H); 8.24 (d, 1H); 8.11 (m, 1H); 8.07 (dd, 1H); 7.97 (m, 3H); 7.86 (d, 1H); 7.80 (s, 1H); 7.78 (dd, 1H); 7.70 (s, 1H); 7.61 (d, 1H); 7.51 (dd, 1H); 4.63 (s, 2H)).

Workup

  1. customThe cool reaction mixture
  2. filtrationfiltered through a Celite pad
  3. washwashed with water
  4. dry with materialThe organic layer was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. concentrationWhile concentrating some crystals
  8. filtrationThe crystals were filtered off
  9. customdried

Sources & evidence

ORD record
ord-4c7e225ba3204cfe9d9da305fd0a5988
Source dataset
uspto-grants-2014_09
Patent number
US08822468B2

Reaction notes

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