Chlorotrimethylsilane → (E)-tert-Butyl 4-(2-(2-(3-methoxyquinolin-2-yl)vinyl)-8-morpholinoimidazo[1,2-b]pyridazin-3-yl)benzoate

HRID 718678Notes

Reaction equation

HRID 718678 reaction equation
[CH:1]([C:3]1[N:4]=[C:5]2[C:10]([N:11]3[CH2:16][CH2:15][O:14][CH2:13][CH2:12]3)=[CH:9][CH:8]=[N:7][N:6]2[C:17]=1[C:18]1[CH:30]=[CH:29][C:21]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])=[CH:20][CH:19]=1)=O.[CH3:31][O:32][C:33]1[C:34]([CH3:43])=[N:35][C:36]2[C:41]([CH:42]=1)=[CH:40][CH:39]=[CH:38][CH:37]=2.C[Si](Cl)(C)C.CCOC(C)=O>CN(C=O)C>[CH3:31][O:32][C:33]1[C:34](/[CH:43]=[CH:1]/[C:3]2[N:4]=[C:5]3[C:10]([N:11]4[CH2:16][CH2:15][O:14][CH2:13][CH2:12]4)=[CH:9][CH:8]=[N:7][N:6]3[C:17]=2[C:18]2[CH:30]=[CH:29][C:21]([C:22]([O:24][C:25]([CH3:26])([CH3:28])[CH3:27])=[O:23])=[CH:20][CH:19]=2)=[N:35][C:36]2[C:41]([CH:42]=1)=[CH:40][CH:39]=[CH:38][CH:37]=2

Participants

6

Reactant 4

HCID 6397ChlorotrimethylsilaneHCID 8857Ethyl AcetateHCID 128209713-Methoxy-2-methylquinolineHCID 117732456tert-Butyl 4-(2-formyl-8-morpholinoimidazo[1,2-b]pyridazin-3-yl)benzoate

Product 1

HCID 117732520(E)-tert-Butyl 4-(2-(2-(3-methoxyquinolin-2-yl)vinyl)-8-morpholinoimidazo[1,2-b]pyridazin-3-yl)benzoate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

To a mixture of compound 5f (100 mg, 0.245 mmol) and 3-methoxy-2-methylquinoline (212 mg, 1.22 mmol) in 4 mL of DMF was added TMSCl (312 μL, 2.45 mmol) dropwise. The resulting mixture was stirred at 90° C. for 24 h. After cooling to rt, the mixture was treated with 60 mL of EtOAc and washed with water (3×20 mL), brine (15 mL) and then dried with Na2SO4, filtered and concentrated. The residue was purified by flash column chromatography on silica gel (0:1-1:9 EtOAc/DCM) to afford compound 63a as a yellow solid. 1H-NMR (CDCl3; 400 MHz) δ 8.10-8.25 (m, 4H), 7.99 (d, J=5.9 Hz, 2H), 7.86 (d, J=8.3 Hz, 2H), 7.68 (d, J=8.1 Hz, 1H), 7.49-7.55 (m, 1H), 7.39-7.47 (m, 1H), 7.37 (s, 1H), 6.11 (d, J=5.6 Hz, 1H), 4.04-4.12 (m, 4H), 3.96-4.04 (m, 4H), 4.01 (s, 3H), 1.64 (s, 9H). Mass spectrum (ESI, m/z): Calcd. for C33H33N5O4, 564.3 (M+H). found 564.5.

Workup

  1. temperatureAfter cooling to rt
  2. washwashed with water (3×20 mL), brine (15 mL)
  3. dry with materialdried with Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by flash column chromatography on silica gel (0:1-1:9 EtOAc/DCM)

Sources & evidence

ORD record
ord-55fa5a9736ee4a20ab0045c1d43cc1e1
Source dataset
uspto-grants-2015_11
Patent number
US09193736B2

Reaction notes

Loading…