Triethylamine hydrochloride → 7-Tert-butyl-6-chloro-3-(2-fluorophenyl)-[1,2,4]triazolo[4,3-b]pyridazine

HRID 986913

Reaction equation

HRID 986913 reaction equation
[Cl:1][C:2]1[N:3]=[N:4][C:5](Cl)=[CH:6][C:7]=1[C:8]([CH3:11])([CH3:10])[CH3:9].[F:13][C:14]1[CH:23]=[CH:22][CH:21]=[CH:20][C:15]=1[C:16]([NH:18][NH2:19])=O.Cl.C(N(CC)CC)C>O1CCOCC1>[Cl:1][C:2]1[C:7]([C:8]([CH3:11])([CH3:10])[CH3:9])=[CH:6][C:5]2[N:4]([C:16]([C:15]3[CH:20]=[CH:21][CH:22]=[CH:23][C:14]=3[F:13])=[N:18][N:19]=2)[N:3]=1

Participants

5

Reactant 3

HCID 11130Triethylamine hydrochlorideHCID 898464-tert-Butyl-3,6-dichloropyridazineHCID 1362882-Fluorobenzhydrazide

Product 1

HCID 111508847-Tert-butyl-6-chloro-3-(2-fluorophenyl)-[1,2,4]triazolo[4,3-b]pyridazineYield 44%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A mixture of 3,6-dichloro-4-(1,1-dimethylethyl)pyridazine (20 g, 0.097 mol), 2-fluorobenzhydrazide (22.6 g, 0.145 mol) and triethylamine hydrochloride (20 g, 0.0145 mol) in dioxan (1.2 l) was stirred and heated at reflux under a stream of nitrogen for 4 days. Upon cooling the volatiles were removed in vacuo and the residue was triturated with dichloromethane (200 ml), filtered and concentrated under vacuum. The residue was purified by chromatography on silica gel eluting with 0%→25% ethyl acetate/dichloromethane to give the title compound (12.95 g. 44%) as a white solid. Data for the title compound: 1H NMR (360 MHz, CDCl3) δ1.57 (9H, s), 7.26-7.35 (2H, m), 7.53-7.60 (1H, m), 7.89-7.93 (1H, m), 8.17 (1H, s); MS (ES+) m/e 305 [MH]+, 307 [MH]+.

Workup

  1. temperatureheated
  2. temperatureat reflux under a stream of nitrogen for 4 days
  3. temperatureUpon cooling the volatiles
  4. customwere removed in vacuo
  5. customthe residue was triturated with dichloromethane (200 ml)
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customThe residue was purified by chromatography on silica gel eluting with 0%→25% ethyl acetate/dichloromethane

Sources & evidence

ORD record
ord-32f104141f544d779861034672e1535e
Source dataset
uspto-grants-2003_10
Patent number
US06630471B1

Linked notes

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