Imidazole → HCID 178450657, compound

HRID 718680Notes

Reaction equation

HRID 718680 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][C:32]1[CH:41]=[C:40]([OH:42])[C:39]2[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=2)[N:33]=1.C[Si](Cl)(C)C.N1C=CN=C1>CN(C=O)C.CCOC(C)=O>[OH:42][C:40]1[C:39]2[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=2)[N:33]=[C:32](/[CH:31]=[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)[CH:41]=1

Participants

7

Reactant 4

HCID 795ImidazoleHCID 6397ChlorotrimethylsilaneHCID 117732456tert-Butyl 4-(2-formyl-8-morpholinoimidazo[1,2-b]pyridazin-3-yl)benzoateHCID 1784288112-Methylquinolin-4-ol

Product 1

HCID 178450657HCID 178450657, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

To a mixture of compound 5f (150 mg, 0.367 mmol) and 2-methylquinolin-4-ol (292 mg, 1.84 mmol) in 4 mL of DMF was added TMSCl (469 μL, 3.67 mmol) dropwise. The resulting mixture was stirred at 90° C. for 16 h. After cooling to rt, the mixture was treated with 60 mL of EtOAc and washed with water (3×20 mL) and brine (15 mL). The solvent was removed in vacuo and the residue was treated with DCM (5 mL). To this mixture was added imidazole (50.0 mg, 0.734 mmol), and the resulting mixture turned clear and was purified by flash column chromatography on silica gel (0:1-1:19 MeOH/DCM) to afford compound 64a as a yellow solid. 1H-NMR (CDCl3; 400 MHz) δ 11.97 (br. s., 1H), 8.26 (d, J=7.8 Hz, 1H), 7.88-8.03 (m, 3H), 7.43-7.83 (m, 6H), 7.22 (t, J=7.5 Hz, 1H), 6.49 (s, 1H), 6.03 (d, J=5.6 Hz, 1H), 3.94 (br. s., 4H), 3.82 (br. s., 4H), 1.55 (s, 9H). Mass spectrum (ESI, m/z): Calcd. for C32H31N5O4, 550.2 (M+H). found 550.5.

Workup

  1. temperatureAfter cooling to rt
  2. washwashed with water (3×20 mL) and brine (15 mL)
  3. customThe solvent was removed in vacuo
  4. additionthe residue was treated with DCM (5 mL)
  5. customwas purified by flash column chromatography on silica gel (0:1-1:19 MeOH/DCM)

Sources & evidence

ORD record
ord-13f9ee2f0a594266b16c7e48655cdcf9
Source dataset
uspto-grants-2015_11
Patent number
US09193736B2

Reaction notes

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