Triethylamine hydrochloride → 7-(Bicyclo[2.2.1]hept-1-yl)-6-chloro-3-phenyl-1,2,4-triazolo[4,3-b]pyridazine

HRID 380318Notes

Reaction equation

HRID 380318 reaction equation
[C:1]12([C:8]3[CH:13]=[C:12](Cl)[N:11]=[N:10][C:9]=3[Cl:15])[CH2:7][CH:4]([CH2:5][CH2:6]1)[CH2:3][CH2:2]2.[C:16]([NH:24][NH2:25])(=O)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.Cl.C(N(CC)CC)C>CC1C=CC(C)=CC=1>[C:1]12([C:8]3[C:9]([Cl:15])=[N:10][N:11]4[C:16]([C:17]5[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=5)=[N:24][N:25]=[C:12]4[CH:13]=3)[CH2:7][CH:4]([CH2:5][CH2:6]1)[CH2:3][CH2:2]2

Participants

5

Reactant 3

HCID 11130Triethylamine hydrochloride2×HCID 11955Benzoylhydrazine2×HCID 183649464-(Bicyclo[2.2.1]hept-1-yl)-3,6-dichloropyridazine

Product 1

HCID 538792557-(Bicyclo[2.2.1]hept-1-yl)-6-chloro-3-phenyl-1,2,4-triazolo[4,3-b]pyridazine

Reagents, catalysts & solvents 1

HCID 7809P-XyleneSolvent

Procedure

A mixture of 4-(bicyclo[2.2.1]hept-1-yl)-3,6-dichloropyridazine (1 g, 4.1 mM), benzoic hydrazide (0.84 g, 6.2 mM) and triethylamine hydrochloride (0.85 g, 6.2 mM) in p-xylene (80 ml) was heated at reflux for 18 hours, after which time more benzoic hydrazide (0.28 g, 2 mM) and triethylamine hydrochloride (0.28 g, 2 mM) were added and the reaction heated at reflux for a further 3 hours. The mixture was allowed to cool, then placed directly onto silica gel for purification by column chromatography using ethyl acetate/hexane mixtures as the eluent. This yielded the title compound (0.38 g, lower Rf of the two isomeric products). 1H NMR (250 MHz, CDCl3) δ1.55-2.06 (8H, m), 2.22 (2H, m), 2.44 (1H, m), 7.25 (3H, m), 8.13 (1H, s), 8.45 (2H, m); MS (ES+) m/e 244 [MH]+.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 18 hours
  3. temperaturethe reaction heated
  4. temperatureat reflux for a further 3 hours
  5. temperatureto cool
  6. customplaced directly onto silica gel for purification by column chromatography

Sources & evidence

ORD record
ord-892002d714aa4bad8b168c1af505e5c3
Source dataset
uspto-grants-2001_10
Patent number
US06303597B1

Reaction notes

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