Triethylamine → 6-Chloro-3-(2-fluorophenyl)-7-(trimethylsilyl)-[1,2,4]triazolo[4,3-b]pyridazine

HRID 1887033

Reaction equation

HRID 1887033 reaction equation
[Cl:1][C:2]1[N:7]=[N:6][C:5]([NH:8][NH:9][C:10](=O)[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[F:17])=[CH:4][C:3]=1[Si:19]([CH3:22])([CH3:21])[CH3:20].BrC(Cl)(Cl)C(Cl)(Cl)Br.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(CC)CC)C>C(#N)C.ClCCl>[Cl:1][C:2]1[C:3]([Si:19]([CH3:22])([CH3:21])[CH3:20])=[CH:4][C:5]2[N:6]([C:10]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[F:17])=[N:9][N:8]=2)[N:7]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 694261,2-Dibromo-1,1,2,2-tetrachloroethaneHCID 15486174N'-(6-Chloro-5-(trimethylsilyl)pyridazin-3-yl)-2-fluorobenzohydrazide

Product 1

HCID 154861756-Chloro-3-(2-fluorophenyl)-7-(trimethylsilyl)-[1,2,4]triazolo[4,3-b]pyridazineYield 97.9%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

Compound 22 (4.1 g, 12.1 mmol) and 1,2-dibromotetrachloroethane (7.9 g, 24.2 mmol) were suspended in acetonitrile (80 mL) and cooled to less than 5° C. Triphenylphosphine (11 g, 30.2 mmol) was added in small portions allowing the reaction to exotherm slightly but keeping the temperature at about 5-7° C. The solids started to dissolve and then a new precipitate began to form. The thick mixture was stirred cold for 15 min. Triethylamine (10 mL, 72.6 mmol) was added dropwise, again allowing an exotherm but keeping the temperature about 5-7° C. The reaction was stirred in an ice-water bath for 1 hr. The mixture was diluted with dichloromethane (200 mL) and washed with water. The organic layer was dried over Na2SO4 and concentrated to a brown liquid. The material was combined with crude material from another (2.9 mmol) reaction and purified on an Analogix automated column chromatography system (SF25-80 g column, 10-40% EtOAc/heptane) to provide 3.8 g (79%) of 23 as a tan, slightly sticky, solid.

Workup

  1. temperaturecooled to less than 5° C
  2. customthe reaction
  3. customat about 5-7° C
  4. dissolutionto dissolve
  5. customto form
  6. customthe temperature about 5-7° C
  7. stirringThe reaction was stirred in an ice-water bath for 1 hr
  8. washwashed with water
  9. dry with materialThe organic layer was dried over Na2SO4
  10. concentrationconcentrated to a brown liquid
  11. customThe material was combined with crude material from another (2.9 mmol) reaction
  12. custompurified on an Analogix automated column chromatography system (SF25-80 g column, 10-40% EtOAc/heptane)

Sources & evidence

ORD record
ord-7ab90d09e8164061a4920c572c0504ec
Source dataset
uspto-grants-2013_08
Patent number
US08501738B2

Linked notes

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