Water → 3-((2-(Methylthio)benzo[d]thiazol-6-yl)methyl)imidazo[1,2-b]pyridazine-6-carbonitrile

HRID 1848252Notes

Reaction equation

HRID 1848252 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.[NH2:17][C:18]1[N:23]=[N:22][C:21]([C:24]#[N:25])=[CH:20][CH:19]=1.O>C(O)CCC>[CH3:14][S:13][C:11]1[S:12][C:8]2[CH:7]=[C:6]([CH2:5][C:2]3[N:23]4[N:22]=[C:21]([C:24]#[N:25])[CH:20]=[CH:19][C:18]4=[N:17][CH:3]=3)[CH:16]=[CH:15][C:9]=2[N:10]=1

Participants

5

Reactant 3

HCID 962WaterHCID 451166946-Aminopyridazine-3-carbonitrileHCID 866810872-Chloro-3-(2-(methylthio)benzo[d]thiazol-6-yl)propanal

Product 1

HCID 866812263-((2-(Methylthio)benzo[d]thiazol-6-yl)methyl)imidazo[1,2-b]pyridazine-6-carbonitrileYield 44%

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 (1.3 g, 4.8 mmol) and 6-aminopyridazine-3-carbonitrile (0.8 g, 7.2 mmol) in 1-butanol (48 mL) was heated at reflux overnight. The mixture was cooled to rt and water (100 mL) was added. The mixture was extracted with EtOAc (3×60 mL, and 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 3-((2-(methylthio)benzo[d]thiazol-6-yl)methyl)imidazo[1,2-b]pyridazine-6-carbonitrile as a yellow solid (0.7 g, 44%). 1H NMR (300 MHz, CDCl3) δ 8.09 (d, J=9.0 Hz, 1H), 7.83-7.78 (m, 2H), 7.69 (s, 1H), 7.36 (d, J=8.4 Hz, 1H), 7.29 (d, J=9.3 Hz, 1H), 4.46 (s, 2H), 2.78 (s, 3H). LCMS (ESI) m/z 338 (M+H)+.

Workup

  1. temperaturewas heated
  2. temperatureat reflux overnight
  3. extractionThe mixture was extracted with EtOAc (3×60 mL
  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-622255f8b2c54fa29155321f7c1df130
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

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