Triphenylphosphine → 4-((6-Chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methoxy)-7-methoxyquinoline

HRID 40176

Reaction equation

HRID 40176 reaction equation
[Cl:1][C:2]1[N:7]=[N:6][C:5]([NH:8][NH:9][C:10](=O)[CH2:11][O:12][C:13]2[C:22]3[C:17](=[CH:18][C:19]([O:23][CH3:24])=[CH:20][CH:21]=3)[N:16]=[CH:15][CH:14]=2)=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C[Si](N=[N+]=[N-])(C)C.CCOC(/N=N/C(OCC)=O)=O>O1CCCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:10]([CH2:11][O:12][C:13]3[C:22]4[C:17](=[CH:18][C:19]([O:23][CH3:24])=[CH:20][CH:21]=4)[N:16]=[CH:15][CH:14]=3)=[N:9][N:8]=2)[N:7]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 78378AzidotrimethylsilaneHCID 5462977Diethyl azodicarboxylateHCID 86630262N'-(6-chloropyridazin-3-yl)-2-(7-methoxyquinolin-4-yloxy)acetohydrazide

Product 1

HCID 250669924-((6-Chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methoxy)-7-methoxyquinoline

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

N′-(6-chloropyridazin-3-yl)-2-(7-methoxyquinolin-4-yloxy)acetohydrazide (2.53 g, 7.0 mmol) was suspended in tetrahydrofuran (50 mL) then added triphenylphosphine (2.8 g, 11 mmol) and trimethylsilyl azide (1.4 ml, 11 mmol). To this suspension, was added diethylazodicarboxylate (2.0 ml, 13 mmol) in rapid drops with a syringe. The mixture became clear and hot to the touch. The reaction mixture was heated at 50° C. for 30 minutes. The reaction mixture was concentrated in vacuo. The remaining oil was triturated with diethyl ether. A gel-like solid formed which was collected on a glass frit, washing with diethyl ether. The solid was then triturated with ethyl acetate, and finally acetonitrile. An amorphous solid formed which was collected on a glass frit, washing with acetonitrile. The solid was further dried under high vacuum. In addition, the ethyl acetate filtrate was concentrated in vacuo. The remaining oil was then triturated with acetonitrile. An amorphous solid formed and was collected on a glass frit, washing with acetonitrile. The solid was further dried under high vacuum affording 4-((6-chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methoxy)-7-methoxyquinoline as a tan solid. MS (ESI, pos. ion) m/z: 342.1 (M+1).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customThe remaining oil was triturated with diethyl ether
  3. customA gel-like solid formed which
  4. customwas collected on a glass frit
  5. washwashing with diethyl ether
  6. customThe solid was then triturated with ethyl acetate, and finally acetonitrile
  7. customAn amorphous solid formed which
  8. customwas collected on a glass frit
  9. washwashing with acetonitrile
  10. customThe solid was further dried under high vacuum
  11. concentrationIn addition, the ethyl acetate filtrate was concentrated in vacuo
  12. customThe remaining oil was then triturated with acetonitrile
  13. customAn amorphous solid formed
  14. customwas collected on a glass frit
  15. washwashing with acetonitrile
  16. customThe solid was further dried under high vacuum

Sources & evidence

ORD record
ord-851298e2ada047858e95d9b75aa367ec
Source dataset
uspto-grants-2013_09
Patent number
US08524900B2

Linked notes

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