Potassium Carbonate → 4-(((6-Methoxy-2-(6-methylimidazo[1,2-b]pyridazin-2-yl)benzofuran-4-yl)oxy)methyl)-2-phenylthiazole

HRID 625135Notes

Reaction equation

HRID 625135 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[O:9][C:8]([C:10]3[N:11]=[C:12]4[CH:17]=[CH:16][C:15]([CH3:18])=[N:14][N:13]4[CH:19]=3)=[CH:7][C:6]2=[C:20]([OH:22])[CH:21]=1.Br[CH2:24][C:25]1[N:26]=[C:27]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[S:28][CH:29]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:21]=[C:20]([O:22][CH2:24][C:25]2[N:26]=[C:27]([C:30]3[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=3)[S:28][CH:29]=2)[C:6]2[CH:7]=[C:8]([C:10]3[N:11]=[C:12]4[CH:17]=[CH:16][C:15]([CH3:18])=[N:14][N:13]4[CH:19]=3)[O:9][C:5]=2[CH:4]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 665984924-(Bromomethyl)-2-phenylthiazoleHCID 867009166-Methoxy-2-(6-methylimidazo[1,2-b]pyridazin-2-yl)benzofuran-4-ol

Product 1

HCID 867009184-(((6-Methoxy-2-(6-methylimidazo[1,2-b]pyridazin-2-yl)benzofuran-4-yl)oxy)methyl)-2-phenylthiazoleYield 66%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
22 °C

Procedure

In a 100 mL round-bottom flask, a suspension of 6-methoxy-2-(6-methylimidazo[1,2-b]pyridazin-2-yl)benzofuran-4-ol (Example 39B, 0.190 g, 0.643 mmol) and 4-(bromomethyl)-2-phenylthiazole (Table of bromides, 0.180 g, 0.708 mmol) in DMF (5 mL) was purged under vacuum and N2 for 10 min. The reaction was treated with potassium carbonate (0.24 g, 1.737 mmol) and stirred at 22° C. for 18 hours, then diluted with DCM and washed with water (1×), brine (1×). The organic layers were dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by silica gel chromatography (2.5×10 cm, 0% to 50% EtOAc in CH2Cl2) to give the impure title material (0.198 g, 66%). The solid was triturated in hot ethyl acetate to provide the pure title material (0.176 g). LC (Method A): 2.414 min. HRMS (ESI) calcd for C26H21N4O3S [M+H]+ m/z 469.1329, found 469.1379. 1H NMR (CDCl3, 400 MHz) δ ppm: 2.57 (s, 3H), 3.84 (s, 3H), 5.39 (s, 2H), 6.46 (d, J=1.96 Hz, 1H), 6.74 (broad d, 1H), 6.91 (d, J=9.1 Hz, 1H), 7.34 (s, 1H), 7.36 (s, 1H), 7.39-7.46 (m, 3H), 7.80 (d, J=9.1 Hz, 1H), 7.90-8.0 (m, 2H), 8.19 (s, 1H).

Workup

  1. customwas purged under vacuum and N2 for 10 min
  2. washwashed with water (1×), brine (1×)
  3. dry with materialThe organic layers were dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel chromatography (2.5×10 cm, 0% to 50% EtOAc in CH2Cl2)

Sources & evidence

ORD record
ord-0be5b58f1aa640318623c0cdaa0e472a
Source dataset
uspto-grants-2016_04
Patent number
US09303065B2

Reaction notes

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