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

HRID 1848164Notes

Reaction equation

HRID 1848164 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.[CH3:17][O:18][C:19]1[N:24]=[N:23][C:22]([NH2:25])=[CH:21][CH:20]=1.O>C(O)CCC>[CH3:17][O:18][C:19]1[CH:20]=[CH:21][C:22]2[N:23]([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:25]=2)[N:24]=1

Participants

5

Reactant 3

HCID 962WaterHCID 816736-Methoxypyridazin-3-amineHCID 866810872-Chloro-3-(2-(methylthio)benzo[d]thiazol-6-yl)propanal

Product 1

HCID 866811336-((6-Methoxyimidazo[1,2-b]pyridazin-3-yl)methyl)-2-(methylthio)benzo[d]thiazoleYield 66.4%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

A stirred mixture of 2-chloro-3-(2-(methylthio)benzo[d]thiazol-6-yl)propanal from Step 4 of Example 117 (600 mg, 2.2 mmol) and 6-methoxypyridazin-3-amine (550 mg, 4.4 mmol) in 1-butanol (20 mL) was heated at reflux overnight. The mixture was cooled to rt and water (40 mL) was added. The mixture was extracted with EtOAc (20 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-methoxyimidazo[1,2-b]pyridazin-3-yl)methyl)-2-(methylthio)benzo[d]thiazole as a light brown solid (500 mg, 66%). 1H NMR (300 MHz, CDCl3) δ 7.79-7.73 (m, 2H), 7.67 (d, J=1.2 Hz, 1H), 7.43 (s, 1H), 7.38 (dd, J=1.5, 8.4 Hz, 1H), 6.64 (d, J=9.6 Hz, 1H), 4.33 (s, 2H), 3.94 (s, 3H), 2.78 (s, 3H). LCMS (ESI) m/z 343 (M+H)+.

Workup

  1. temperaturewas heated
  2. temperatureat reflux overnight
  3. extractionThe mixture was extracted with EtOAc (20 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-9a444fc3d15049e48f34b85b1a161cc8
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

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