Water → 6-((6-Chloroimidazo[1,2-b]pyridazin-3-yl)methyl)-2-(methylthio)benzo[d]thiazole

HRID 1848186Notes

Reaction equation

HRID 1848186 reaction equation
Cl[CH:2]([CH2:5][C:6]1[CH:16]=[CH:15][C:9]2[N:10]=[C:11]([S:13][CH3:14])[S:12][C:8]=2[CH:7]=1)[CH:3]=O.[Cl:17][C:18]1[N:23]=[N:22][C:21]([NH2:24])=[CH:20][CH:19]=1.O>C(O)CCC>[Cl:17][C:18]1[CH:19]=[CH:20][C:21]2[N:22]([C:2]([CH2:5][C:6]3[CH:16]=[CH:15][C:9]4[N:10]=[C:11]([S:13][CH3:14])[S:12][C:8]=4[CH:7]=3)=[CH:3][N:24]=2)[N:23]=1

Participants

5

Reactant 3

HCID 962WaterHCID 216436-Amino-3-chloropyridazineHCID 866810872-Chloro-3-(2-(methylthio)benzo[d]thiazol-6-yl)propanal

Product 1

HCID 866811546-((6-Chloroimidazo[1,2-b]pyridazin-3-yl)methyl)-2-(methylthio)benzo[d]thiazoleYield 84%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

A mixture of 2-chloro-3-(2-(methylthio)benzo[d]thiazol-6-yl)propanal from Step 4 of Example 117 (1.5 g, 5.5 mmol) and 6-chloropyridazin-3-amine (1.4 g, 11 mmol) in 1-butanol (60 mL) was heated at reflux overnight. Then the mixture was cooled to rt and water (120 mL) was added. The mixture was extracted with EtOAc (60 mL×3). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with 50:1 to 20:1 DCM/MeOH to afford 6-((6-chloroimidazo[1,2-b]pyridazin-3-yl)methyl)-2-(methylthio)benzo[d]thiazole as a yellow solid (1.6 g, 84%). 1H NMR (300 MHz, CDCl3) δ 7.89 (d, J=9.6 Hz, 1H), 7.81 (d, J=8.4 Hz, 1H), 7.68 (dd, J=0.6, 1.2 Hz, 1H), 7.53 (s, 1H), 7.37 (dd, J=1.8, 8.4 Hz, 1H), 7.03 (d, J=9.3 Hz, 1H), 4.40 (s, 2H), 2.78 (s, 3H). LCMS (ESI) m/z 347 (M+H)+.

Workup

  1. temperaturewas heated
  2. temperatureat reflux overnight
  3. extractionThe mixture was extracted with EtOAc (60 mL×3)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel chromatography
  9. washeluting with 50:1 to 20:1 DCM/MeOH

Sources & evidence

ORD record
ord-e7e30208352b44db9bde8d376db0754d
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

Loading…