Phosphorus oxychloride → 6-((6-Phenyl-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methyl)quinoline

HRID 40244

Reaction equation

HRID 40244 reaction equation
[N:1]1[C:10]2[C:5](=[CH:6][C:7]([CH2:11][C:12](O)=O)=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.C(Cl)(=O)C(Cl)=O.[C:21]1([C:27]2[N:32]=[N:31][C:30]([NH:33][NH2:34])=[CH:29][CH:28]=2)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.P(Cl)(Cl)(Cl)=O>CN(C=O)C.C(Cl)Cl.C1(C)C=CC=CC=1>[C:21]1([C:27]2[CH:28]=[CH:29][C:30]3[N:31]([C:12]([CH2:11][C:7]4[CH:6]=[C:5]5[C:10](=[CH:9][CH:8]=4)[N:1]=[CH:2][CH:3]=[CH:4]5)=[N:34][N:33]=3)[N:32]=2)[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1

Participants

9

Reactant 4

HCID 24813Phosphorus oxychlorideHCID 65578Oxalyl chloride2×HCID 64098423-Hydrazinyl-6-phenylpyridazineHCID 117887092-(Quinolin-6-yl)acetic acid

Product 1

HCID 249683686-((6-Phenyl-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methyl)quinoline

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 1140TolueneSolvent2×HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
100 °C

Procedure

To a 50 ml round-bottomed flask was added 2-(quinolin-6-yl)acetic acid (0.60 g, 3.2 mmol), CH2Cl2 (20 ml) and oxalyl chloride (4.0 ml, 8.0 mmol, 2 M in CH2Cl2) and DMF (0.2 mL of a solution of 1 drop DMF in 1 mL CH2Cl2). After 3 d, an additional 2.5 eq. of oxalyl chloride was added. After 4 h, toluene (1 mL) was added and the mixture was concentrated. Toluene (3 mL) was added and again concentrated. The residue was taken up in CH2Cl2 (20 mL) and 1-(6-phenylpyridazin-3-yl)hydrazine (0.60 g, 3.2 mmol) was added. The mixture was stirred for 17 h and then concentrated. The mixture was then taken up in phosphorous oxychloride (20 ml, 220 mmol) and heated at 100° C. for 15 h. Toluene (5 mL) was added and the solution was concentrated. Another 5 mL toluene was added to the residue and once again it was concentrated. The brown solid residue was taken up in sat. NaHCO3 and extracted with EtOAc (4×150 mL) and 25% iPrOH/CHCl3 (3×150 mL). The combined extracts were washed with brine, dried (Na2SO4) and concentrated onto silica. Purification by silica gel chromatography (0 to 5% MeOH (2M in NH3)/CH2Cl2) afforded the title compound as a tan solid. MS (ESI, pos. ion) m/z: 338 (M+1).

Workup

  1. waitAfter 4 h
  2. concentrationthe mixture was concentrated
  3. additionToluene (3 mL) was added
  4. concentrationagain concentrated
  5. concentrationconcentrated
  6. concentrationthe solution was concentrated
  7. additionAnother 5 mL toluene was added to the residue and once again it
  8. concentrationwas concentrated
  9. extractionextracted with EtOAc (4×150 mL) and 25% iPrOH/CHCl3 (3×150 mL)
  10. washThe combined extracts were washed with brine
  11. dry with materialdried (Na2SO4)
  12. concentrationconcentrated onto silica
  13. customPurification by silica gel chromatography (0 to 5% MeOH (2M in NH3)/CH2Cl2)

Sources & evidence

ORD record
ord-4bef37be58384b8c8c5d332988e3a4c0
Source dataset
uspto-grants-2013_09
Patent number
US08524900B2

Linked notes

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