Water → 6-(Imidazo[1,2-b]pyridazin-3-ylmethyl)-2-(methylthio)benzo[d]thiazole

HRID 1848148Notes

Reaction equation

HRID 1848148 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.[N:17]1[CH:22]=[CH:21][CH:20]=[C:19]([NH2:23])[N:18]=1.O>C(O)CCC>[N:23]1[CH:3]=[C:2]([CH2:5][C:6]2[CH:16]=[CH:15][C:9]3[N:10]=[C:11]([S:13][CH3:14])[S:12][C:8]=3[CH:7]=2)[N:18]2[C:19]=1[CH:20]=[CH:21][CH:22]=[N:17]2

Participants

5

Reactant 3

HCID 962WaterHCID 230373AminopyridazineHCID 866810872-Chloro-3-(2-(methylthio)benzo[d]thiazol-6-yl)propanal

Product 1

HCID 866811196-(Imidazo[1,2-b]pyridazin-3-ylmethyl)-2-(methylthio)benzo[d]thiazoleYield 81.8%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

A stirred mixture of 2-chloro-3-(2-(methylthio)benzo[d]thiazol-6-yl)propanal (500 mg, 1.8 mmol) from Step 4 of Example 117 and pyridazin-3-amine (350 mg, 3.6 mmol) in 1-butanol (20 mL) was heated at reflux for 15 h. The mixture was cooled to rt and water (40 mL) was added. The mixture was extracted with EtOAc (20 mL×3) and the combined organic layers were washed with brine. The organic layer was separated, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography eluting with 2 to 5% MeOH in DCM to afford 6-(imidazo[1,2-b]pyridazin-3-ylmethyl)-2-(methylthio)benzo[d]thiazole (460 mg, 80%) as a light brown solid. 1H NMR (300 MHz, CDCl3) δ 8.32 (dd, J=4.5, 1.5 Hz, 1H), 7.94 (dd, J=9.3, 1.5 Hz, 1H), 7.79 (d, J=8.7 Hz, 1H), 7.66 (s, 1H), 7.58 (s, 1H), 7.36 (dd, J=8.4, 1.8 Hz, 1H), 7.02 (m, 1H), 4.45 (s, 2H), 2.77 (s, 3H); LCMS (ESI) m/z 313 (M+H)+.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 15 h
  3. extractionThe mixture was extracted with EtOAc (20 mL×3)
  4. washthe combined organic layers were washed with brine
  5. customThe organic layer was separated
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel flash chromatography
  10. washeluting with 2 to 5% MeOH in DCM

Sources & evidence

ORD record
ord-ee2d38ae249e4a8599011b0902e2c2bd
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

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